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Full text of "American journal of pharmacy"

S Scientific Library 




UNITED STATES PATENT OFFICE 



Case 



M. 



6%?<3C>?0&?<3t>?<5C>?<3C>?<3C>?<)C>?<]C>?0[>?<)C>% 



J J, to / 7 

THE 

american 
Journal of Pharmacy 

PUBLISHED BY AUTHORITY OF THE 

PHILADELPHIA COLLEGE OF PHARMACY 

EDITED BY 

HENRY KRAEMER 

— *M jxxM^T 

PUBLICATION COMMITTEE FOR 1914 

SAMUEL P. SADTLER M. I. WILBERT 

JOSEPH W. ENGLAND CHARLES H. LaWALL 

JOSEPH P. REMINGTON JOHN K. THUM 

AND THE EDITOR 



VOLUME 86 



PHILADELPHIA 
1914 



THE AMEEIOAN 



JOURNAL OF PHARMACY 



JANUARY, 1Q14 



THE ASSAY OF MERCURIC CHLORID TABLETS. 

^^^_^B/Robert M. Chapin, 
Bureau of AmmaTlndustry, U. S. Department of Agriculture. 

At the present time mercuric chlorid tablets, especially those 
prepared after the well-known Wilson formula, are very widely 
used, and are used moreover with implicit confidence in the accuracy 
of their declared content of mercuric chlorid under circumstances 
whic*h render such accuracy a matter of considerable importance to 
individual welfare and to the public health in general. There can 
be no question of the desirability of assay methods which shall be 
fairly accurate, yet simple and rapid enough to be freely used by 
manufacturers, pharmacists, hospitals, and sanitary officials at a 
minimum of expense and chemical equipment. 

Several years ago Rupp 1 proposed a rapid method for the deter- 
mination of mercury in various compounds, involving the following 
steps : ( 1 ) Reduction to metallic mercury by formaldehyde in alkaline 
solution in presence of potassium iodid ; (2) solution of the precipi- 
tated mercury in excess of standard iodin solution after acidification 
with acetic acid ; and (3) titration of excess iodin by standard sodium 
thiosulphate. A modification of the method is now official in the 
German Pharmacopoeia for the assay of tablets composed of mer- 
curic and sodium chlorids. 

In this country Smith 2 has thoroughly studied the Rupp method 
when applied to pure mercuric chlorid,. obtaining, when certain modi- 

1 Rupp, E. Ueber die volumetrische Bestimmung des Quecksilbers. Be- 
richte der Deutschen Chemischcn Gesellschaft, Vol. 39, No. 14, pp. 3702-3704. 
Berlin, Nov. 10, 1906. 

2 Smith, Carl E. Volumetric determination of mercury. American 
Journal of Pharmacy, Vol. 83, No. 7, pp. 311-315. Phila., July, 191 1. 

(1) 



2 



Mercuric Chi or id Tablets. 



f Am. Jour. Pharm. 
\ January, 1914. 



fications were introduced, a recovery of 99.8 to 100.3 P er cent - of the 
mercuric chlorid employed. Smith's modifications involved (1) 
the use of a larger amount of substance and reagents to 
reduce experimental errors, (2) a longer time of action by 
formaldehyde to insure complete reduction to metallic mercury, 
and (3) a much less degree of acidification before addition of iodin, 
since large amounts of free acetic acid tend to produce low results. 
Smith states that similarly good quantitative results were obtained 
when the method was applied to mixtures of mercuric chlorid and 
ammonium chlorid colored with aniline dyes. That is, the modified 
method is implied to be applicable to commercial tablets prepared 
after Wilson's formula (mercuric chlorid, 7.3 grains; ammonium 
chlorid, 7.7 grains; coloring matter, q.s.). 

In this laboratory Smith's statements and results were con- 
firmed on solutions of pure mercuric chlorid. Utter failure, however, 
followed attempts to apply his method either to commercial tablets or 
to similar laboratory mixtures of mercuric and ammonium chlorids. 
Abnormal precipitates appeared after addition of iodin, and results 
obtained were erratic and much too low. At the same time the method 
given in the German Pharmacopoeia, slightly modified, was found 
to work smoothly and quantitatively. 

The addition of formaldehyde to a solution of ammonium salts 
produces hexamethylenamin, which is known to form difficultly solu- 
ble compounds with both iodin and mercuric salts. 3 In Smith's 
modification, then, conditions appear to be such as to permit the 
formation and separation of hexamethylenamin compounds to the 
resultant vitiation of the process, while in the method of the German 
Pharmacopoeia the greater dilution at which the process is worked 
either inhibits the formation of such interfering substances, or, more 
probably, is sufficient to retain them in solution and hence in a harm- 
less condition. At all events, if, in addition to other minor modifi- 
cations later to be noted, a volume of 75 c.c. of water is added at 
the time the contents of the flask are acidified before the addition of 
iodin, no abnormalities appear in the working of Smith's process, 
and the results are equally accurate in the presence or absence of 
ammonium chlorid. 

Inasmuch as the method finally chosen here as most satisfactory is 

3 Cohn, G. Die Verbindung des Urotropins. Pharmazeutische Zentral- 
halle, Vol. 52, No. 44, pp. 1173-1179. Dresden, Nov. 2, 191 1. 



Am. Jour, pharm. | Mercuric Chlorid Tablets. 

January, 1914. j 



3 



somewhat different in details from either of the two modifications 
already noted, the points of difference and the reasons therefor will 
be discussed. 

In the first place, while it is true that the use of large amounts 
of substance and reagents tends to reduce the relative magnitude of 
experimental errors, there is a point beyond which any slight possible 
gain in accuracy is attained only at the sacrifice of an unwarranted 
measure of simplicity, convenience, and rapidity. It is certainly open 
to question whether this point is not passed by Smith's modification 
with its considerable consumption of standardized solutions, espe- 
cially when the total volume of liquid worked with is increased by 
the 75 c.c. of water here found necessary to prevent interference by 
hexamethylenamin compounds. The writer therefore recommends 
the employment of 0.20 to 0.25 gram of mercuric chlorid for each test, 
and the addition of 25 c.c. of tenth-normal iodin. 

Experiment 1. — To test the limits within which the results of parallel 
determinations may fall if the above proportions are used, a series of seven 
parallel tests were made on a solution of commercial tablets, using the equiva- 
lent of one-half tablet for each test. Aside from the use of volumetric 
apparatus which had passed the requirements of the Bureau of Standards, no 
precautions not employed in ordinary quantitative work in any laboratory 
were observed. The cubic centimetres of iodin solution (tenth-normal X 
0.978) consumed in the solution of mercury were as follows: (1) 17.72; 
(2) 17.73; (3) 17.68; (4) 17.69; (5) 17.72; (6) 17.73; (7) 17-65; an extreme 
difference of 0.08 c.c. The average weight of mercuric chlorid per tablet was 
therefore found to be from 0.4677 to 0.4698, a difference of 0.45 per cent. 
The range of variation reported by Smith in a series of five tests by his 
method on pure mercuric chlorid was 0.5 per cent. 

Secondly, the proportion of potassium iodid should be consider- 
ably increased over that employed by either Rupp or Smith in order 
to avoid the formation of mercurammonium compounds which result 
when caustic alkali in excess is added to a solution containing potas- 
sium mercuric iodid and ammonium salts, as in the well-known 
" Nessler test." 

Thirdly, the presence of ammonium salts in one way or another 
operates to retard the reduction to metallic mercury so that it is not 
complete in 5 minutes though apparently so after 10 minutes. 

Lastly, commercial formaldehyde solutions often contain foreign 
substances, some of which conceivably may consume iodin, and in 
fact such solutions have here been found which did possess this 



4 



Mercuric Chlorid Tablets. \ A ™- Jour - ftj*- 

l January, 1914. 



power in slight but distinct degree. Hence a standard thiosulphate 
solution should be made the basal standard against which the iodin 
solution is standardized by running a blank assay with the other 
solutions and reagents intended for actual use. 

The method finally chosen for tablets after Wilson's formula is 
as follows : Weigh 5 tablets, dissolve in water, dilute to 100 c.c, and 
pass through a dry filter, discarding the first 20 c.c. of filtrate. From 
the remainder pipette 10 c.c. (equivalent to one-half tablet) into a 
glass-stoppered 250 c.c. Erlenmeyer flask, add 2 l / 2 grams pure pow- 
dered potassium iodid, mix to entirely dissolve, and then wash 
down the sides of the flask with 20 c.c. of normal caustic alkali. 
Add exactly 3 c.c. of 37 per cent, formaldehyde solution, mix 
thoroughly, and let stand for at least ten minutes, swirling the 
flask occasionally. Then wash down the sides of the flask with 
a mixture of 5 c.c. of 36 per cent, acetic acid with 25 c.c. water; mix, 
and without delay run in from a burette 25 c.c. of tenth-normal 
iodin while constantly swirling the flask. Stopper the flask tightly, 
shake vigorously for three minutes, then after giving the contents a 
final swirling motion leave at rest for two minutes. If then no undis- 
solved mercury can be detected at the bottom the stopper is removed, 
rinsed, together with the neck of the flask, with a stream from a 
wash-bottle, and the excess iodin titrated with tenth-normal sodium 
thiosulphate, adding starch solution only when the iodin is nearly 
consumed. 

Standardize the iodin solution by running a blank assay on 10 c.c. 
distilled water. 

Subtract the volume of thiosulphate solution used in the assay 
from that used in the blank. The difference multiplied by the factor 
0.0271 for strictly tenth-normal sodium thiosulphate will give the 
average weight of mercuric chlorid per tablet. For a direct check 
upon the value of the sodium thiosulphate solution run an assay on 
10 c.c. of a 2.y 2 per cent, solution of mercuric chlorid of known 
purity. 

While mercuric chlorid is the important active ingredient of tab- 
lets made according to Wilson's formula, nevertheless ammonium 
chlorid is an essential part of the formula, added in order to render 
the tablets easily soluble and to inhibit the formation of insoluble, 
and hence inactive, compounds of mercury. An assay of such tablets 



Am. jour, pharm. \ Mercuric Chlorid Tablets. 5 

January, 1914. j ^ 

ought therefor to include an estimation of ammonium chlorid, espe- 
cially when a simple and convenient method is available. 

The method for ammonium chlorid here adopted is an adaptation 
of the process of Ronchese, 4 which is based on the reaction between 
formaldehyde and a neutral ammonium salt, whereby methylenamin, 
(CH 2 ) fi N 4 , is formed, the acid originally contained in the ammo- 
nium salt being released and becoming titratable with standard 
caustic alkali and phenolphthalein. The strengths of reagents, etc., 
recommended by Wilkie 5 have been adopted. 

Titration by standard alkali and phenolphthalein can not of 
course be conducted in presence of mercuric chlorid. This difficulty, 
however, is easily overcome by throwing the mercury into a complex 
ion through the addition of potassium iodid. The method is as fol- 
lows : Into each of two 150 c.c. Erlenmeyer flasks pipette 5 c.c. (one- 
fourth tablet) of the tablet solution previously prepared for the esti- 
mation of mercuric chlorid (5 tablets per 100 c.c.) and add to each 
flask 2 c.c. of a 20 per cent, solution of potassium iodid. 

Dilute one volume of 37 per cent, formaldehyde solution with 
three volumes of water, measure 20 c.c. of the mixture into a small 
flask, add 0.5 c.c. of phenolphthalein indicator solution, neutralize 
with tenth-normal barium hydrate or caustic alkali, then flow the 
solution over the sides of one of the flasks (flask A) containing tablet 
solution, and mix well. To the other flask (flask B) containing tablet 
solution add about 65 c.c. water. 

Now add to flask A 25 c.c. water and titrate with tenth-normal 
barium hydrate or tenth-normal caustic alkali free from carbon 
dioxid until, by using flask B as a standard for comparison, a color 
change is perceptible (titration A). 

Add methyl red to flask B and titrate with either tenth-normal 
acid or alkali as needed (titration B). 

To titration A add titration B if performed with acid, or subtract 
if performed with alkali. The resultant figure multiplied by the 
factor 0-.0214 for strictly tenth-normal alkali will give the average 
weight of ammonium chlorid per tablet. 

4 Ronchese, A. Nouveau procede de dosage de rammoniaque. Journ. de 
Pharmacie et de Chimie, Vol. 25, No. 12, pp. 611-617. Paris, June 16, 1907. 

5 Wilkie, John M. The Ronchese method of determining ammonia and 
its extension to the determination of the total acid content of organic am- 
monium salts and ammoniacal solutions. Journal of the Society of Chemical 
Industry, Vol. 29, No. 1, pp. 6-7. London, Jan. 15, 1910. 



6 Mercuric Chlorid Tablets. { A j^™£ P mT' 

For a direct check upon the value of the tenth-normal alkali run 
an assay upon 5 c.c. of a 2]/ 2 per cent, solution of pure ammonium 
chlorid. 

Solutions, reagents, and water used should be free from carbon 
dioxid. 

Ordinarily titration B is very small, sometimes zero, but usually 
calling for the addition of a few drops of tenth-normal acid. 

As respects the end points with the indicators it is only possible 
to state that up to the present time no blue or green tablets which 
have been received by the writer have presented the slightest difficulty. 
The characteristic colors of the indicators of course do not appear in 
the presence of other coloring matter, but the change of tint, if 
standards of comparison are used, is delicate and distinct. No red 
tablets have been received for examination. 

The reliability of the method may be shown by noting a few 
results. 

Experiment 2. — Four tests made on 5 c.c. of a solution of 2 grams each 
of commercial CP. chlorids of mercury and ammonium per 100 c.c. gave the 
following figures for titration A (titration B — O), made with barium hydrate 
solution (tenth-normal X 1.021) which had been standardized against a labora- 
tory stock solution of half-normal hydrochloric acid: (1) 18.24 c.c; (2) 18.26 
c.c; (3) 18.29 cc -'> (4) 18.26 c.c; an extreme difference of 0.05 c.c. and a 
recovery of 99.6 to 99.9 per cent, of the ammonium chlorid employed. 

Experiment 3. — Three titrations made on 5 c.c. of the solution of commer- 
cial tablets employed in Experiment 1 gave titration B as zero, and titration 
A as (1) 22.64 c.c; (2) 22.58 c.c; (3) 22.62 c.c; an extreme difference of 
0.06 c.c 

It appears, therefore, that assay methods are now available for 
accurately and conveniently estimating mercuric and ammonium 
chlorid in commercial tablets. Knowing the weight of tablets taken 
to prepare the stock solution for assay, estimation of coloring matter 
and " filler " is merely a matter of subtraction. Further possible 
tests, such as degree of solubility, amount of insoluble matter, and 
uniformity of weight of individual tablets, are a matter of discretion 
with the analyst and need no discussion. 



A January m™' \ Resistance of Guinea Pigs to Poisonini 



SEASONAL VARIATIONS IN THE RESISTANCE OF 
GUINEA PIGS TO POISONING BY OUABAIN AND BY 
liquid' PREPARATIONS OF DIGITALIS. 

By C. C. Haskell, A.B, M.D. 

In a previous paper 1 it has been shown that guinea pigs are more 
resistant to poisoning by ouabain during certain months of the year 
than at others. These results were confirmed in a general way by 
Vanderkleed and Pittenger 2 in a subsequent publication. It is of 
interest to compare the results secured in this laboratory with those 
reported by Vanderkleed and Pittenger. 

I have used male pigs exclusively, and have been compelled to 
employ animals differing largely in weight; the majority, however, 
weighed 250 grams or more, so it seems best to compare my results 
with those obtained by Vanderkleed and Pittenger using " large 
males." In order to facilitate comparison, the average minimum 
lethal dose has been expressed in fractions of a gram per gram body 
weight and put in the following tabular form : 

Table I. 



Month. 


Vanderkleed and Pittenger. 


Haskell. 


January 


. 1912 


.OOOOOO25 


.OOOOOO52 + 


February 


1912 


. OOOOOO30 


.OOOOOO37 


March. 


. . 1912 


.OOOOOO32 


. OOOOOO36 


April 


1912 


. OOOOOO33 


. OOOOOO4O 


May 


1912 


. OOOOOO33 


. OOOOOO45 


June 


1912 


. OOOOOO33 


. OOOOOO4O 


July 


. .1911 


. 0000002 I 










August 


1911 


. 0000002 1 


. OOOOOO29 


September 


. . 191 1 


. 0000002 I 


. OOOOOO30 


October 


1911 


. 0000002 1 


. OOOOOO36 


November 


1911 


. OOOOOO24 


. OOOOOO52 


December 


1911 


.OOOOOO28 


.OOOOOO52 



It is readily seen that the same general conclusion is deducible 
from both series of tests : the resistance of the pigs is least during the 
hot summer months and greatest in the cooler weather. In August, 
there is a difference of 38 per cent, between the lethal dose required 

1 Am. Jour. Pharm., Vol. 84, No. 6, p. 241, 1912. 

2 Jour. Am. Ph. Assoc., Vol n, No. 5, P- 558, 1913- 



8 Resistance of Guinea Pigs to Poisoning {^^"J 



Pharm 
1914. 



in Indianapolis and that determined in Philadelphia ; and in January, 
the enormous preponderance of 108 per cent, is shown by the In- 
dianapolis lethal dose. Obviously, it is scarcely to be expected that 
we should secure very closely comparable results in assaying a galeni- 
cal if such divergence occurs in testing a " pure principle." 

In endeavoring to account for this disagreement, the technic em- 
ployed should be closely scrutinized. It is a well-recognized fact 
that testing digitalis upon frogs requires the closest attention to 
details and necessitates the avoidance of any disturbing factors such 
as large variations in the weight of the animals and, especially, ex- 
tremes of temperature. From previous statements of those who 
have employed the guinea pig method, one is led to infer that such 
extreme caution is not necessary when this method is used, and the 
results of Vanderkleed and Pittenger seem to show that weight and 
age are factors of little moment. 

In all of my experiments, a solution of ouabain, I to 10,000 in 25. 
per cent, alcohol, was used. Vanderkleed and Pittenger do not state 
whether alcohol was present in the solutions they employed, but its 
absence would explain the smaller dose determined by them as 
compared to the dose I found necessary in August, because alcohol 
exerts a similar antagonistic action toward the absorption of subcu- 
taneously-administered ouabain as it does toward digitalis adminis- 
tered in this way. Some other explanation, however, is necessary to 
account for the difference between the minimum lethal dose deter- 
mined in Indianapolis in January (.00000052 -(-) and that determined 
in Philadelphia for the same month (.00000025). The pigs used by 
Vanderkleed and Pittenger were kept in fairly warm quarters ; while 
our animals were subjected to considerable variations in temperature, 
the thermometer occasionally registering as low as 50 F. This, I 
believe, has an important bearing on the resistance of the guinea pigs 
and, together with the influence of the alcohol used in my experi- 
ments, may serve to explain the difference in the lethal dose as 
determined in the winter months. 

Since this earlier report, the minimum lethal dose of ouabain 
in 25 per cent, alcohol has been determined upon guinea pigs in a 
number of different months and a comparison is of some interest. 
In Table II such a comparison is given. 

These figures indicate that the temperature influences the powers 
of resistance. During the extremely cold winter of 1911-12 the 



* January ^iST' } Resistance of Guinea Pigs to Poisoning. 9 

dose for November, r^. fiber, and January was .00000052: while 
during the much milder winter of 191 2-1 3, the lethal dose was 
smaller. Where comparison is possible in other months, the differ- 
ence never amounts' to more than 15 per cent. 



Table II. 



Month. 



January. . . 
February. . 

March 

April 

May 

June 

July 

August 

September 
October. . . 
November. 
December. 



IOII. 



. 00000029 
00000030 
, 00000036 
, 00000052 
. 00000052 



1912. 



, 00000052 + 
.00000037 
, 00000036 
. 00000040 
. 00000045 
. 00000040 



.00000036 
. 00000042 
. 00000040 
. 00000045 



00000040 
00000042 

.00000037 
. 00000045 

.00000025 
.00000025 



Seasonal variations in the resistance of test animals may be 
obviated by the use of a satisfactory standard, and Vanderkleed and 
Pittenger suggest the use of ouabain when galenicals of the " heart 
tonic " group are tested upon guinea pigs. The use of ouabain is 
justified, however, only when it has been shown that the variations 
in the resistance toward poisoning by ouabain parallels that toward 
poisoning by the galenicals under consideration. Opportunity has 
occurred to determine the minimum lethal dose of a small number 
of samples of tincture and fluid extract of digitalis at different seasons 
of the year. Some of the tinctures were made by the U.S. P. method 
and some were made with a menstruum containing 75 per cent, alco- 
hol. All of the fluid extracts were made with a menstruum contain- 
ing 70 per cent, or 80 per cent, alcohol. 

In testing the tinctures, portions were evaporated to a semi- 
solid consistence upon the water-bath and the residue suspended in 
an amount of distilled water equal to the original volume of the 
portion taken for evaporation. The same procedure was followed 
with the fluid extracts, save that the volume of distilled water was 
five times that of the fluid extract taken. For reasons that will be 
apparent later; it is desirable that the preparations be divided into 
two groups ; one comprising preparations containing about 50 per 



io Resistance of Guinea Pigs to Po«onitt^.j A Jj™J llTI.™' 

cent, alcohol ; the other comprising those containing from 70 to 80 
per cent, alcohol. 

The comparison of the lethal doses for two tinctures made with 
50 per cent, alcohol and the lethal dose for ouabain during the same 
months is given in Table III. N 



Table III. 





June, 1912. 


Oct., 1912. 


Dec, 1912. 


Jan., 1913. 


Aug., 1913. 


Ouabain 

Tr. Digitalis U. S. P. 

434900 

Tr. Digitalis U. S. P. 

457579 


. OOOOOO4 
.004 


. OOOOOO42 
.004 


. OOOOOO45 
.007 + 
.0075 


. OOOOOO4 
.OO65 


.00000025 

.OO42 

.0052 











So far as can be judged by this limited number of experiments, 
" seasonal " variations in the resistance of guinea pigs toward poison- 
ing by ouabain and by tinctures of digitalis made with 50 per cent, 
alcohol follow the same general curve. In January, 1913, the lethal 
dose for Tincture 434900 was .0065, while in July, 1913, it showed a 
decrease of 35.4 per cent.: the lethal dose of ouabain showed a 
decrease of 37.5 per cent, during the same time. In December, 1912, 
the dose of Tincture 457579 was .0075, while in July, 191 3, it was 
30.6 per cent, less: the dose of ouabain suffered a decrease of 44 
per cent. 

In testing the preparations containing relatively high percentages 
of alcohol, entirely different results were obtained. These are so 
surprising that it was only after confirming them repeatedly that I 
could feel that they were not due to some error in testing. The tests 
were carried out in a manner exactly similar to those dealing with 
the tinctures just discussed and the difference in the behavior seems 
to depend upon an essential difference in the composition of prepara- 
tions made with 50 and 75 per cent, alcohol respectively. 

From these results, it is evident that no seasonal variation has 
been observed in the resistance of guinea pigs to poisoning by fluid 
preparations of digitalis made by percolation of the leaf with men- 
strua containing 70 to 80 per cent, alcohol. Tinctures made with 
75 per cent, alcohol differ in several important points from those 
made with 50 per cent, alcohol, but it seems almost incredible that 
the resistance of guinea pigs to poisoning by the two should follow 



Am. Jour. Tharm. } 
January, 1914. j 



M agma 



B ism ut hi. 



1 1 



Table IV. 





Ouabain 1 


Tr. Digi- 
talis 
471124 


Tr. Digi- 
talis 
46 10 1 1 


Tr. Digi- 
talis 
467056 


Tr. Digi- 
talis 2 
24678 


F. E. Digi- 
talis 
461015 


F. E. Digi- 
talis 
1654092 


Jan. 1912 

1913 
Feb. 1912 

1913 
Mar. 1912 

1913 
Apr. 1912 

1913 
May 1912 

1913 
June 1912 

1913 
July 1912 

1913 
Aug. 19 1 2 

1913 
Sept. 1912 

1913 
Oct. 1912 

1913 
Nov. 1912 


52 
40 

37 
42 

36 






.OO24 


.0025 
.0025 














.OO27 










40 
37 
45 
45 
40 

25 
29 
25 

42 
40 

45 






.0030 

.0025 

.0025 
.0025 












.00022 


.OOO47 


.0025 


.0020 


.OO23 








.OOO23 


.OOO32 


1913 
Dec. 1912 

1913 




.0022 















1 The figures in this column represent fractions of a gram to the eighth decimal 

(.00000052). 

2 Alcohol not removed from this tincture. 



such different lines. A confirmation of these observations would cer- 
tainly suggest that careful pharmacological study of digitalis prepara- 
tions made with different menstrua would not entail a waste of time. 
From the Laboratory of Experimental Medicine, Eli Lilly and 
Company, Indianapolis, Aug. 26, 1913. 



MAGMA BISMUTHI. 

By S. Bertha Muller, P.D., 
Assistant Pharmacist at the German Hospital, Philadelphia. 

In recent years Magma Bismuth has become quite popular, so 
much so that it was deemed advisable to make the preparation 
official. 

With that end in view several formulas have been proposed and 
duly tried out, but in our experience have not proved generally 
satisfactory. 



12 



Magma Bismuthi. 



IAm. Jour. Pharm. 
j January, 1914. 



The formulas proposed direct ammonia water to be used to pre- 
cipitate the bismuth nitrate. This, in our experience, leads to con- 
siderable trouble trying- to wash the resulting Magma free from the 
excess of ammonia. It takes a great deal of water to do so and even 
if one has succeeded in getting the final washings to no longer react 
with phenolphthalein the Magma itself will always give a strong 
reaction. To reduce the amount of ammonia water leads to a reaction 
in the opposite direction, giving a decided acid reaction which causes 
the gradual solution of the bismuth hydroxide. Furthermore, when 
the Magma is poured on a strainer for the purpose of washing it, 
the surface of the Magma very soon develops a metallic coating 
which certainly points to a decomposition going on and may be due 
to exposure to air. Unfortunately this is the only way the Magma 
can be washed because distilled water has the property of causing 
the Magma to curdle into large flaky masses, taking up considerable 
water and holding it so that it is utterly impossible to get the Magma 
to settle in order to wash it by decantation, thus preventing undue 
exposure to air. 

Attention should also be drawn to the fact that the amount of 
bismuth subnitrate used, results in too thick a Magma. Further- 
more, 80 grams of bismuth subnitrate cannot be satisfactorily dis- 
solved in 60 c.c. of nitric acid. It takes i c.c. of nitric acid for every 
gram of bismuth subnitrate to be dissolved. 

However, with some modifications the proposed official formula 
will give satisfactory results. In the first place the amount of 
bismuth should be somewhat reduced, then ammonium carbonate 
should be substituted for ammonia water, and lastly, distilled water 
containing i-iooo sodium chloride should be used. By using am- 
monium carbonate the resulting Magma is not nearly so alkaline, it 
will not react with phenolphthalein but will and should react alkaline 
toward methyl orange. It therefore does not require nearly so much 
washing. It only needs to be washed until it is practically tasteless. 
The use of this small amount of sodium chloride in distilled water 
prevents the curdling of the Magma, and it therefore can readily be 
washed by decantation, no strainer being required. After sufficient 
washing it is allowed to settle to the required volume, which usually 
takes about a week. 

Spigot water can also be used in place of distilled water if it has 
been previously boiled with i per cent, magnesium carbonate for 



A j;,mTry/i9i4 m "} Books as a Source of Disease. 13 

about 15 minutes, then cooled and filtered and 1-1000 sodium chloride 
added. 

The following formula has been fairly satisfactory : 

Bismuth Subnitrate 50.0 

Nitric Acid 50.0 

Ammonium Carbonate 80.0 

Distilled water to make 1000.0 

Dilute the nitric acid with an equal volume of water and dissolve 
the bismuth subnitrate in it, dilute further to 300 c.c. and filter 
through cotton. 

Dissolve the ammonium carbonate in 3000 c.c. distilled water 
containing 1-1000 sodium chloride and filter. 

Pour the acid solution slowly and with constant stirring into 
the alkaline solution. When the resulting precipitate has subsided, 
decant the supernatent liquor and wash by decantation until the 
Magma is practically tasteless, using distilled water containing 
1-1000 sodium chloride. Then allow to settle to 1000 c.c. 

When tested the Magma should react alkaline toward methyl 
orange. 

BOOKS AS A SOURCE OF DISEASE. 

By William R. Reinick. 

I do not for a moment want anyone to think that I am endeavor- 
ing to prove that books, as fomites, are so dangerous that they 
should be shunned like the plague, but simply to show that books, 
especially when greasy or moist fingers are placed upon the pages 
and covers, are excellent hiding grounds for bacteria, both pathogenic 
and non-pathogenic, and that the same care should be used as in 
handling other objects of like character. 

Is Such Transmission Possible? 

As far as our exact knowledge of books and papers as a source 
of danger is concerned, we, at the present time, have very little 
evidence, but what we have proves beyond question, that disease may 
be contracted by this means. ( )n the other hand there are many 
reputable physicians who claim that transmission by this means is 
an impossibility, due to the fact that the organisms could not exist 



14 



Books as a Source of Disease. 



< Am. Jour. Pharm. 
( January, 1914. 



for any length of time under such adverse conditions. A statement 
of this character is generally made by one who only has a superficial 
knowledge of the subject, especially in its biological aspect. The 
apparatus needed to properly conduct experiments upon bacteria 
is quite expensive, and generally, the young physician who has just 
graduated has the time and possesses the enthusiasm to undertake 
these researches, but not the capital, and then when he has the 
means, he has so many patients that he cannot spare the time. 

Another trouble is the extreme difficulty which arises when one 
is prepared to study this subject. On account of the great surface 
covered by the pages of the books, it means a long and tedious series 
of experiments, and even then, on account of their being invisible to 
the eye, one is not sure that he has obtained every speck of life that 
may be on the paper. 

The knowledge that we are now acquiring as to the great resist- 
ance of these small forms of life to adverse conditions of climate 
and atmosphere, their resistance to degrees of heat, their wonderful 
adaptability to rapid changes of environment, food, and their power 
to remain dormant for a period more or less unknown at the present 
day, their ability to form a protective coat, which prevents pene- 
tration when placed in material that would otherwise destroy them, 
all these points indicate that we may be on the wrong track in using 
the present means of eradication. And furthermore, in making our 
laboratory tests we are forced to isolate the colonies, giving conditions 
foreign to their natural state of existence, and also the difficulty in 
separating them into distinct species. 

Newman states as follows : " A word may be said here respecting 
the much-discussed question of species of Bacteria. A species 
may be defined as ' a group of individuals,' which, however many 
characters they share with other individuals, agree in presenting one 
or more characters of a peculiar and hereditary kind with some cer- 
tain degree of distinctness. Now, as regards bacteria, there is no 
doubt that separate species occur and tend to remain as separate 
species. It is true, there are many variations, due in large measure 
to the medium in which the organisms are growing — variations of 
age, adaptation, nutrition, etc. — yet the different species tend to 
remain distinct. Involution forms occur frequently, and degenera- 
tion invariably modifies the normal appearance. But because of the 
occurrence of these, morphological and even pathological differences 
of environment and physical conditions must have marked effect 



Am. Jour. Pharm. ) 
January, 1914. j 



Books as a Source - of Disease. 



15 



upon such sensitive units of protoplasm as bacteria ; it has recently 
been proven that one great reason why modification occurs in pure 
artificial culture is that the species has been isolated from amongst 
its colleagues and doomed to a separate existence. One of the most 
abstruse problems in the immediate future of the science of bacteri- 
ology is to learn what intrinsic characters there are in species or 
individuals which act as a basis for the association of organisms for 
a specific purpose. Some bacteria appear to be unable to perform 
their regular function without the aid of others. An example of 
such association is well illustrated in the case of tetanus, for it has 
been shown that if the bacilli and spores of tetanus alone obtain en- 
trance to a wound, the disease may not follow the same course as 
when with the specific organism of lactic acid bacilli, or the common 
organisms of suppuration or putrefaction also gain entrance. Again, 
the virulence of other'bacteria is also increased by means of associa- 
tion. The bacilli coli is an example, for, in conjunction with other 
organisms, this bacilli, although normally present in health in the 
alimentary canal, is able to set up acute intestinal irritation, and 
various changes in the body of an inflammatory nature." 

Among the higher forms of life we have, in a few hundred of 
years, recognized natural changes, or often brought the change about 
by artificial selection. Now if a change, quite noticeable, can be 
made during a period of years, in forms which do not produce more 
than one or two generations a year, what changes are able to take 
place, in forms capable of producing a new generation every twenty 
or thirty minutes, and these changes invisible to us? 

Another source of failure to obtain positive results is due to the 
fact that conclusions are generally arrived at from twenty-four 
hour tests ; and, if there is no result within that period, the experi- 
ment is marked negative and the material destroyed. 

Very little information of value, to help in deciding whether or 
not books act as carriers, was received from the various Boards of 
Health of the United States. A circular letter requesting a list of 
cases, the source of which was traced to books and papers, was 
sent to the Boards of Health of each State and forty-one cities. 
Answers were received from only ten States and nineteen cities, 
about 30 per cent, of the total number of letters sent. 

With these replies no cases were given, although some of the 
officials stated it to be their belief that diseases were contracted 
through contact with books, while others ridiculed such a possibility. 



16 Books as a Source of Disease. { A Tanuiry 191T' 

Quite a number of physicians have sent me histories of cases, which 
they have observed during their practice. 

The medical and library periodicals are constantly printing 
notices about disease being contracted from books, and as in the 
case of the theory of insects transmitting disease germs, at first 
ridiculed, but now acknowledged to be true by the most skeptical, 
so are books now passing through the same criticism. 

Diseases Claimed to Have Been Traced to Books. 

Scarlet Fever. — Dr. J. Allen Palmer, of Erie, Kansas, notes a 
case of scarlatina developing in a girl, living in a town where there 
had been no cases of the disease for months, nor had she been 
exposed to personal contact. Investigation showed that the patient 
had received a letter a few days previous to the appearance of the 
rash, from a child living some sixty miles from her, who was just 
recovering from scarlatina. Another case of transmission was traced 
by Dr. Howard W. Lyon, of Chicago. In this instance a little girl 
living in Chicago contracted scarlatina from being allowed to handle 
a letter just received from a home in Minneapolis, where one of the 
family had the disease. 

Dr. A. Maverick, of San Antonio, Texas, sent the following case : 
A boy convalescent from scarlet fever read a book from the public 
library and used as book-marks strips of skin peeled from his hands 
and feet. Unknown to the physician, the book was returned to the 
library by a servant of the household with no attempt at sterilization 
or even removing the pieces of skin. During the next month, two 
boys in different families who borrowed the book from the library, 
caught scarlet fever and one died from the disease. 

Diphtheria. — Dr. Robert Britton, of Downsville, New York, 
writes of two cases in 1902, one of the patients dying, and as there 
were no cases of the disease in the neighborhood, the question arose 
where had the children contracted the infection. Questioning re- 
vealed, that on account of the weather and conditions of the road 
they did not attend school on March 27, but played in a house 
having a garret, in which were stored some old school books which 
had been taken from an old farm-house on this farm — in which in 
i860 had occurred six cases of diphtheria, four of which were fatal 
in forty-eight hours. 

Small-pox. — Small-pox is one of the most contagious diseases, 
and few who are exposed escape infection. The contagion exists in 



Am. jour, pharm. > Books as a Source af Disease. 17 

January, 1 ( J14. J ' / 

the pustules, in the fluid of the body, and apparently in the ex- 
halation from the lungsand skin. The dried scales thrown off during 
desquamation are the most important element in disseminating the 
malady, and is often communicated, through the medium of clothes, 
furniture, books, etc., which have come in contact with patients. 

Dr. P. A. Jordan, of San Jose, California, states the following: 
A man, a great reader, continuously used books from a circulating 
library located in a neighboring town in which there was an epidemic 
of small-pox, and later developed a severe form of small-pox. 

Blood-Poisoning. — Dr. Emericus Karacson, while making a trans- 
lation of a Turkish Manuscript, in one of the Mosques in Turkey, 
had his fingers soiled with some of the mould which covered the old 
musty tomes, and accidentally touched a cut on his face ; a few weeks 
later his face swelled up, causing him intense pain. A quick opera- 
tion relieved him of this and his face regained its normal size, and 
he soon resumed his work, apparently in perfect health. About a 
month later he was taken ill with fever and treated first for influenza, 
then for typhoid fever. His condition growing worse, a Hungarian 
physician was sent for, who diagnosed the case at once as blood- 
poisoning, caused no doubt by the fungi that had entered the patient's 
system through the abrasion on the face, and he died within a few 
days. 

Venereal Diseases. — That the danger to man from what are called 
the " social evil " diseases, after exacting a cost in human life and 
physical disability beyond computation, and the necessity of using 
means which will prevent its spread, is now recognized, as seen by 
the numerous societies being formed to furnish speakers and publish 
literature upon the subject, thus forcing the public to face the question 
as it has never been done before. 

A list of articles found to be carriers of the germs of gonorrhea, 
the one most likely to be contracted through contact, would include 
every article of domestic and public use, and even the hands of the 
unclean and ignorant may transfer the germs to the articles. A num- 
ber of cases have been traced to books. 

Diseases, besides these mentioned, have been named as being 
transmitted by books, and there is no reason to doubt that the germs 
of other diseases found on fomites will also be found on books. 
The bacillus of anthrax, which occurs in cattle, must certainly be 
found on the leather bindings, as it is frequently transmitted through 



?8 



Books as a Source of Disease. 



(Am. Jour. Pharm. 
\ January, 1914. 



abrasions of the hands in cases of those who have the occasion to 
handle infected wools and hides. 

Tuberculosis. — The number of bacilli in the sputum of a person 
suffering from tuberculosis is enormous. Nuttall estimated that a 
person moderately advanced in the disease, expectorated between two 
and four billions of bacilli every twenty-four hours. One having this 
disease does not at once become helpless, and in the meantime the 
patient generally spends a great deal of his spare time reading, and 
as this disease usually causes the one inflicted to cough a great deal, 
often involuntarily, it is but natural that particles of the sputum will 
be caught on the paper of the books, ready to be transmitted to 
another victim. 

Dust. — I do not think that enough study has been given to the 
bacteria found in dust, as far as public institutions are concerned. 
Careful consideration of the examinations already made of dust from 
various sources, especially in the industrial trades during the past 
few years, will show at once that the health is often affected by the 
impurities found in the air inhaled, and that the purifying of this 
air is of greatest importance from a sanitary standpoint. Besides the 
danger from exposure to the so-called diseases, the germs of 
which are stated to be borne in the air, the pollution of the air by 
organic and inorganic dust is beyond a doubt the cause of a great 
deal of ill-health, and death. 

An analysis made by Prof. Charles H. Lawall of dust collected by 
me at the State Library of Florida, at Tallahasse, off of books that 
had not been disturbed for many years, gave the following result: 

" Ash (inorganic material, mainly sand), 54.90 per cent. 

" Organic matter consists of much unidentifiable matter, in which, 
however, could be distinguished microscopically the following : wood 
fragments, cotton, linen, silk, wool (some of them dyed bright 
colors), hairs of various kinds, both plant and animal, starch grains, 
spore and an occasional yeast cell. No evidence was found of 
arsenic or mercury or other poisonous metals or their compounds, 
except what might be called a faint trace of arsenic, which was traced 
by a method so delicate as to detect arsenic in almost any substance 
from which it has not been specifically removed." 

Dr. McFadden and Mr. Lunt seem to prove the paucity of 
bacteria in very dusty air. The evidence otherwise available is 
entirely conclusive that the risk to disease infection is much greater 
indoors than out in the open, where the germs are exposed to the 



Am. Jour. Pharm. 1 Books dS d Source Off Disease. IQ 

sunlight, which is a great factor in keeping the germs in an inactive 
state. ' j 

But, besides the danger of infection from inhaling disease germs 
found in the dust, there is also to be considered that it is the cutting 
edges of the particles of dust, which when inhaled scratch or cut the 
delicate air passages leading to the lungs and also the lungs them- 
selves. The finer dust will not, perhaps, act as quickly as the coarser 
grains, but it means that the evil result will take a much longer time 
before making its appearance. 

It is known that those who spend most of their time in outdoor 
occupations, generally have better health than those who are com- 
pelled to work in factories, offices, etc., and the first thought of sani- 
tary science to-day is the elimination of dust. 

It is extremely difficult, in fact almost impossible, to trace many 
cases of infection on account of the long period between the first 
infection and the appearance of the disease in a form to demand 
medical attention. 

Dr. Hugh H. Brown, of Washington, D. C, and an assistant, in 
1907, moved a large number of books which had not been disturbed 
for quite some time. Within a few days both contracted severe colds, 
characterized by distinct bubbling, and a severe cough accompanied 
by a feeling of compression and pain in the chest, and an exceed- 
ingly profuse and purulent expectoration of a deep yellow color the 
consistency of thick cream. The cold lasted about two weeks. 

Vitality of Bacteria. — Before considering the mode of overcom- 
ing these organisms, consideration should first be given to their 
power of resistance to disinfection, sterilization, etc. 

Bacteria exist in nature in three states : 

( 1) As adult or fully-developed and active microorganisms, with 
all the characteristics of parasites. 

(2) As spores or reproductive cells endowed with latent life. 

(3) As desiccated germs, whose vital principle had been sus- 
pended but not destroyed ; which, when placed in a moist and suitable 
environment, possess the power of resuscitation. 

" The air germs," says Professor Tyndall, " differ much among 
themselves in their tendency to development ; there are some which 
are young and there are others which are old, some dry and some wet. 
The same water infected by those germs requires more or less time 
to develop bacterial activity. This explains the difference in the 
rapidity with which epidemic diseases act upon different persons. 



20 



Books as a Source of Disease. 



/Am. Jour. Pharm. 
I January, 1914. 



In certain cases the period of incubation, if it can be so called, is long-, 
in others it is short; the difference is the result of the different 
degrees of preparedness of the contagious matter, and I personally 
believe that the health of the person infected has most to do with the 
appearance or non-appearance of a disease." 

The length of time that the different pathogenic bacteria can 
withstand drying varies greatly. Krausz placed bacteria from 48- 
hour old cultures in books and kept them in the dark at room tem- 
perature. He found that cholera lived only 40-95 days and tubercle 
bacilli 80-103 days. Other investigations confirm his results except 
in the cases of tuberculosis and diphtheria. Abel found that diph- 
theria bacilli retained their virulency on toys for six months and 
this is the length of time that Von Scham gives. Lion and Von 
Schab both say that tubercle bacilli withstand drying from six to 
nine months. 

The number of bacteria that may be found on much-used books 
was investigated by Lion. A novel from a public library varied from 
250 .bacteria per 100 square centimetres on the middle of a clean 
page to 1,250, 1,875, and 3,350 on the dirty edges. A college atlas 
showed from 650 to 1,075 P er 100 square centimetres; an anatomy 
book 2,275 to 3,700. The bindings were by far the richest in bacteria, 
yielding on an average of 7,550 per square centimetre. 

As to the pathogenic bacteria that may occur on books, the follow- 
ing investigations are of great interest. Krausz inoculated seven 
guinea pigs with dirty pieces of paper from much-used books and 
they all died of peritonitis. The eighteen inoculated with pieces from 
clean books remained healthy. Du Cazal and Catrin found Staphy- 
lococcus pyogenes on an old book in a hospital. Most striking of all 
are Mitelescu's experiments. He took 60 much-used books that had 
been in a public library from six months to two years ; he cut out the 
dirtiest parts, soaked them in salt solution, centrifuged the liquid 
and inoculated guinea pigs with the sediment. Nineteen died of 
septicemia, and twelve of streptococcus infection. He repeated the 
experiment with thirty-seven books from three to six years old. 
Fourteen of the guinea pigs died of septicemia, and fifteen contracted 
tuberculosis. The damp dirt on the older books was a good medium 
for tubercle bacilli. 

The following abstracts are taken from the report made to the 
Board of Trustees of the Chicago Public Library upon books in that 



A j» 1 mai r ,, P i'il4 m 'J Boohs as a Source of Disease. 21 

• 

library by Dr. W. A. Kuflewski and are of value as showing the 
germs to be found on books long in use. 

These books were selected by Mr. F. H. Hild, Librarian, and 
Dr. Reynolds, the object being to get the books that were most worn 
and most soiled, and the examination was made by Dr. Adolph 
Gehrmann, who reported as follows : 

D 2017a From delivery station, 14 years. 

19 Cultures from page 57, brown spot — negative. 

Cultures from torn places on cover. <' 

(A) Staphylococci and saprophytes. 

(B) Negative. 

C 7357 Delivery station, 20 years. 

Cultures from title page — negative. 

Cultures from title page — negative. 

Cultures from page 19 — negative. 

Cultures from page 19 — negative. 

H 2455c Delivery station, 6 years. 

Cultures from top of page 278 — negative. 
Cultures from leather back — Staphylococcus pyogenes albus. 
Cultures from bottom edge of pages — Staphylococcus pyogenes 
albus. 

Cultures from top edge of pages — saprophytes and S. pyogenes. 

F 8346c Circulating department, 2 years: Popular juvenile. 
Cultures from leather back — negative. 
Cultures from top of pages — negative. 
Cultures from page 190 — negative. 

F 494aa Circulating department, 26 years : Popular fiction. 
Cultures from spot on page 25 — negative. 
Culture from leather back — negative. 
Cultures from bottom pages — negative. 

RR 281 Buck's Cyclopaedia, 14 years : Reference book. 

Cultures from leather back— 1 colony of Staphylococci. 
Cultures from edge of cover — 1 colony of Staphylococci. 
Cultures from dirty page — Staphylococci. 
Cultures from clean pages — Staphylococci. 

Summary of Results. 
Negative results : 3 books — C 735 ; 58 346c ; and E 494aa. 

Cultures from covers showing Staphylococci: 3 books — D 2017a, H 2455c, and 

281. 
1 

Cultures from pages showing Staphylococci: 2 books — H 2455c and RR281. 

I 



22 Books as a Source of Disease. { A m™" 

A series of cultures from the hands of two persons in the labora- 
tory were made in the same manner and these showed a few colonies 
of saprophytes and Staphylococci pyogenes albus. In a general 
way these cultures were similar to those giving positive results made 
from the books. 

The method employed in making these cultures was to take a few 
drops of sterile bouillon and with a platinum wire rub it upon the 
place from which the inoculations were made and then transfer this 
loop of bouillon to the blood serum boxes used by the department 
for diagnosis of diphtheria. These were placed in an incubating 
oven for forty-eight hours. The resulting colonies were examined 
microscopically. 

Control cultures were made on several boxes by first placing the 
drop of bouillon on the sterile slide and then transferring it to the 
blood serum media. 

In none of the cultures were diphtheria bacilli found. The 
Staphylococcus pyogenes albus is one of the pus bacteria usually 
found upon the skin of most individuals. The saprophytes are 
accidental non-pathogenic bacteria from the air, and are of no 
consequence. 

Dr. Kuflewski states that " after personal investigation and ex- 
amination of three sets of books taken at random from the shelves 
of the Chicago Public Library I am prepared to state that I found 
bacteria in large numbers in all the samples and that each book 
was more or less infected. These bacteria were in large numbers 
and were both pathogenic and non-pathogenic— the word pathogenic 
meaning ' disease-producing.' " 

In many instances these bacteria do not harm, not even the 
pathogenic, because of the resistance of the tissue — being unimpaired 
— or because of the comparatively small numbers of bacteria which 
gain access to the tissues ; but under favorable circumstances, such 
as a simple exposure to cold and especially to bronchitis, which is so 
prevalent in Chicago, a little wound or an abrasion of the surface 
of the body, a little scratch of the mucous membrane or of the 
skin-, which as we all know is often treated as insignificant and is 
neglected, may be the means of introduction into the system of the 
most infectious disease germs. It is well known that a fresh wound 
absorbs bacteria and their toxins very rapidly. 

I have had in my own experience a case in which I satisfactorily 
proved that a child contracted an infectious disease in the eye, from 



A ja/wy ^914"'} Books as ct Source af Disease. 23 

the page of a book. Prof. Dr. W. A. Evans, who is an authority, 
states the case of a person who was infected with typhoid germs from 
books, which case was established beyond question. I had another 
case two or three years ago ; a gentleman who was suffering from 
cancer in the roof of the mouth, in which the tongue and lips were 
also affected, was reading books from public libraries in this city 
for nearly two years and until I was called to treat him. He had 
been treated before by the " faith cures " and by the followers of 
Dowie. This patient was found expectorating minute pieces of his 
tongue and lips, which were a cancerous tissue, all over the pages 
of the book he read. That they were cancerous was not only proven 
by my own examination, but by that of Dr. LeCount, an eminent 
bacteriologist, who reported to me that the piece of tissue submitted 
was cancerous, containing' cancerous cells. 

Of course I prohibited this person from reading any more books 
from the libraries, and told his wife to be very careful as the disease 
was contagious. 

In my own experiments I had no difficulty in obtaining colonies 
from the pages and bindings of all of the books examined, and I also 
obtained cultures of various forms from dust many years old, which 
according to the text-books, should have been destroyed. 

Flies. — These insects are now known to carry germs. In some 
cases as many as six million have been found on a single specimen. 
In very few cases are libraries protected by screens ; the fly just from 
a patient suffering from a contagious disease, or off the waste matter 
in a near-by cesspool, has easy access to the interior of the library, 
where, alighting upon a binding or page of an open book it proceeds 
to eject a number of germs with its excreta, or by rubbing its body 
with its forelegs, shakes large numbers orf, which find ready lodge- 
ment, especially if the spot where the rubbing takes place is greasy, 
as is generally the case where a book has been much used or circu- 
lated for quite a number of times. 

People do not seem able to overcome the vulgar habit of moisten- 
ing the fingers in turning over the leaves of the books and again plac- 
ing the finger on the lips each time to remoisten, never considering 
that each time he is, perhaps, transferring germs to fertile soil for 
propagation, resulting in sickness later on, or in case of a patient 
already suffering from disease, especially tuberculosis, helping to 
inflict another victim with the disease. And we all know that sick 



24 



Books as a Source of Disease. 



i Am. Jour. Pharm. 
\ January, 1914. 



persons, especially in the convalescent stage, spend a great deal 
of their time in reading books and magazines. 

Disinfection. — This process in killing germs in books, although 
recommended, especially by those who have the disinfectants and the 
apparatus for sale, may be dismissed as of very little use, on account 
of the impossibility of the gases penetrating into the interior of the 
volumes, and in no case, even if the entire surface is reached, will 
they remove all of the spores. 

Sterilisation. — Both steam and hot air sterilization are of little 
value for books, because the first will cause the paper of the books 
to absorb the moisture, swell and deform the book, and while in the 
case of hot air sterilization, the heat would, by drying up all the 
moisture in the books, have the same effect, besides, in the case of 
books bound with leather, cause the leather to stretch and often 
break. 

The heat also will absorb the moisture and the paper will become 
dry and brittle, lessening the life of the volume. At present I do 
not believe, that there is any method which may be depended upon 
to entirely eliminate the possibility of diseases being contracted 
through contact with fomites, such as books and the hundreds of 
other articles in daily use, constantly being transferred to a sick- 
room, returned and ready for another victim. I believe that some 
of the State Boards of Health are now beginning to recognize the 
futility of quarantining and disinfecting. Instead they are spending 
all their energies in improving sanitary conditions as to the necessity 
of cleanliness and the proper care of health. If a person using books 
or any other of the numerous articles named as conveying germs will 
use precautions as to the degree of cleanliness of the article they 
handle, and will take the proper care of their health, they need have 
no fear of contracting any disease by means of a book or any other 
article. 

Suppose that a library did disinfect their books, what claim can 
they make that the book has no germs, after it has been placed on a 
shelf next to another book or been handled by a reader or one of the 
assistants. Dr. A. W. Doty, of New York City, states along the line 
of using disinfectants at intervals, " I know of nothing in public 
sanitation which is more farcical than the general or periodical dis- 
infection of books with gaseous disinfectants for the purpose of 
preventing infection. These agents have no penetration of any 
account, and I have little faith in them for this purpose. I believe 



Am. Jour. Pharm. ) 
January, 1914. / 



Ehrlich's Chemotherapy. 



25 



that the careful dusting of the books and an abundance of fresh air 
and proper ventilation in a library is all that need be done under 
ordinary conditions." 

He here touches the remedy, cleanliness, in relation to the books, 
but the same care that should be given to keeping the books clean 
should also be insisted upon for the employees and readers of libraries 
and all places where dust may accumulate. 

A visit to almost any library will generally show, by placing the 
hands in back of the books upon the shelves, that there is a great deal 
of dust lying there. Very few libraries, even those recently erected, 
have had the vacuum system, which seems to be almost perfected, 
installed. Instead of making the reader wash his or her hands before 
using a book, it is very difficult for one to obtain access to the lava- 
tory to wash his hands even if he so desires. In fact, there are some 
libraries which have no lavatories at all for the public. 

Books are often placed on shelves in stacks, poorly ventilated and 
lighted. The results obtained in the library at Hawaii, whose books 
were constantly being destroyed by insects while stored in a dark, 
badly ventilated building, but was almost eliminated when transferred 
to a well-lighted and ventilated building, prove the value of pure air 
and sunlight. Not disinfectant plants, but sunlight, fresh air, the 
elimination of dust, and the proper cleanliness on the part of the 
employees and readers, is the way, not only to prevent books from 
becoming fomites, but also the people becoming carriers in this age 
of prevention. 



EHRLICH'S CHEMOTHERAPY. 1 

How His Logical, Systematic Campaign Against Certain 
Diseases Has Demonstrated the Value of Scientific 
Methods in Therapeutical Problems. 

By Henry P. Talbot. 

Chemotherapy has been called " a new science.'' It should, 
rather, be regarded as the designation of a scientific field in which 
therapeutics and chemistry intermingle in the solution of problems 
involving the principles of both of the older sciences, much as do 
physics and chemistry in so-called " physical chemistry/' which is 
not, on that account, regarded as a " new " science. 

1 Reprinted from Science Conspectus, March, 1913. 



26 



Ehrlich's Chemotherapy. 



( Am. Jour. Pharm. 
I January, 1914. 



Therapeutics is defined as that branch of medical science " which 
deals with the composition, application, and modes of operation of 
the remedies for disease." But it has now taken on a somewhat 
broader, though less exact, meaning, and is understood to include 
the general administration of medicine, questions of hygiene and 
dietetics, and much that has to do mainly with the general well- 
being of the individual. That chemistry must be, as it has been for 
centuries, inseparable from the study of therapeutics is obvious, 
and the advance from the simplicity of the theory of Geber, accord- 
ing to which the animal organism was made up of only " sulphur " 
and " mercury " to our still very imperfect knowledge of the com- 
plex changes of physiological processes is, indeed, remarkable. But 
modern medical and chemical science is not content with the mere 
alleviation of the ravages of existing disease, that is, with the modify- 
ing or assisting of functions temporarily disturbed, but has struck 
more directly at the root of the trouble by devising means actually to 
destroy the causative agents and thus arrest the disease, or to render 
the animal organism inhospitable to these causative agents, as, for 
example, through the anti-toxins and the methods of preventive 
medicine in general. 

All this had been done even before the advent of chemotherapy. 
What, then, is new about this combination of scientific effort in two al- 
lied fields ? Essentially this : It is a logical, systematic campaign against 
diseases which are caused by the infection of the animal organism 
by parasites (i.e, bacteria or protozoa) by means of chemicals which 
have not been found by empirical and more or less haphazard 
methods, but have been synthesized and built up solely for the pur- 
pose in hand, and as the result of researches which have called for 
the highest type of accurate observation and analytical reasoning 
for their execution. In this way it has been found possible to devise 
means by which the animal organism can be sterilized with respect 
to the parasites in question, and the consequent symptoms of disease 
can be arrested. 

The development of this field is due almost entirely to Professor 
Paul Ehrlich, of Frankfort, and his co-workers. Dr. Ehrlich was 
educated as a physician, but has now become also one of the most 
accomplished and able investigators in the field of synthetic organic 
chemistry. A conception of the significance of his work can, perhaps, 
be best obtained by noting important phases in its progressive de- 
velopment. 



A January P i9i4 m * } Eltrlich's Chemotherapy. 27 

More than thirty years ago Ehrlich began using coal-tar colors in 
his physiological studies, employing them as stains for preparations 
to be examined under the miscroscope. It is, of course, now com- 
monly known that certain dye-stuffs appear to have a selective 
affinity for certain tissues of the body, or for certain parasites when 
residing within it, and these stains are in every day use by the 
pathologist. But it was not so thirty years ago, and Ehrlich first 
found that a dye-stuff known as methylene-blue, and its congeners, 
were the only colors which would stain live nerve tissue, and drew 
from this the important inference, which is at the basis of chemo- 
therapy, that this was because of a particular receptivity for these 
dye-stuffs on the part of these tissues or parasites. It is easy to 
understand something of the importance of this use of these stains, 
or dyes, if it is recalled that the changes produced in the individual 
cells or tissues by drugs are not detectable even under the micro- 
scope in most cases, and that it is only through these stains that a 
knowledge of what has actually happened can be even approximately 
learned. 

Ehrlich concluded from his observations that it was probable that, 
since these tissues and parasites possessed this receptivity for these 
specific bodies, there must be some definite effect produced as a re- 
sult of the combination, if combination it were, and proceeded to 
conduct investigations in this direction. After some time these 
researches were rewarded, and in 1890 Ehrlich and Lappmann pub- 
lished a paper on the pain-relieving properties of methylene-blue, 
and, later, Ehrlich and Guttmann found that the same dye was fatal 
to one type of the plasmodium, the parasite which causes malaria. 
As the latter field of investigation, that of the effect upon parasites, 
appeared very promising, they turned their attention to a particular 
class of parasites known as trypanosomes, because these could be 
more easily studied by the inoculation of mice. 

The disease-producing parasites are sometimes of vegetable 
origin, as the bacteria, and sometimes of animal nature, as the pro- 
tozoa. The trypanosomes are worm-like bodies, somewhat larger 
than bacteria, belonging to the animal class, and the diseases which 
they produce prevail most generally in tropical countries. Of these 
diseases, surra, most generally known in India among cattle, dogs 
and camels; nagana (tsetse-fly disease), known in Africa among 
animals in general; and mal de cadaras, known in South America 
among horses, are typical, while man is also attacked by the sleeping 



28 Ehrlich's Chemotherapy. { ^ January, wu™' 

sickness in the tropics. The scourge of syphilis is produced by a 
parasite known as the spirochete, which is closely allied to the others 
named, although it is still undetermined whether its nature is animal 
or vegetable. As will be seen, this particular disease has been found 
to be one of the most amenable to treatment. 

As a result of his researches, Ehrlich formulated a theory regard- 
ing the behavior of the cells of living tissue, or of parasites toward 
foreign bodies. He conceives them as made up of a central " dom- 
inant body," which throws out " sidechains," to which he later 
gave the name receptors. These are of variable character, some 
being nutrient receptors, and others chemo-receptors, that is, recep- 
tors or certain definite chemical elements or groups of elements, 
known in chemistry as radicals. In a crude sense, the receptors 
may be likened to locks, and the nutrient or chemical bodies as keys, 
each fitting a particular lock, as, for example, the dyestuff methy- 
lene-blue already mentioned. The combinations thus affected may 
be beneficial to the cell, as in the case of the nutrients, or they may 
result in the poisoning and death of the cell, as in the case of the 
methylene-blue when brought into contact with the type of Plas- 
modium referred to above, or quinine for plasmodia in general, a 
specific remedy for malaria discovered by empirical research. 

Ehrlich and his co-workers, with extraordinary skill and industry, 
prepared several hundred dye-stuffs, studying the varying effects 
of alterations in chemical structure, each new compound having been 
logically selected as the result of laboratory tests of its parasiticidal 
efficiency. Of all these, very few finally withstood severe tests, pos- 
sibly not more than ten in all, but the fact was established that it was 
possible in certain cases to sterilize the animal organism with respect 
to parasites, by this means, without, at the same time, poisoning the 
animal itself. They were also able to establish certain principles as 
to the chemical structure of the dye-stuffs most likely to be effective. 
They encountered, however, many difficulties. A dye which would 
attack and destroy a given parasite in a particular animal would not 
always do so in another species. Symptoms of disease would some- 
times recur after varying intervals, and the parasites would then 
often exhibit peculiar resistance to further attack. 

While these researches were still in progress, Uhlenmuth and 
Salmon published an account of instances of marked success in the 
destruction of the spirochete of syphilis, and the arrest of the disease, 
by the use of an arsenical compound known as atoxyl. Secondary 



A januTry P i h 9i4 m '} Ehrlich' s Chemotherapy. 29 

and seriously harmful effects to the patients were, however, the 
consequence of this treatment, but the parasiticidal properties of 
this compound were so marked that Ehrlich turned his attention to 
it, in an attempt to so modify its effects upon the animal organism 
which was harboring the parasites, that its curative power might be 
made available. 

The task was by no means a simple one. He first established the 
composition of the atoxyl as a para-amido-phenyl arsenic acid. The 
vast amount of work already done with the dye-stuff indicated certain 
lines of probable success, which, nevertheless, was only attained on 
the synthesis of the six hundred and sixth organic compound by 
Ehrlich and Kata, sometimes known as " 606," and now designated 
salvarsan. Chemically it is dioxy-diamido-arseno-benzol, in which 
arsenic is associated with structural groups akin to those found in 
the dye-stuffs. A later preparation " 914," known as neo-salvarsan, 
is said to be a combination of a salvarsan with sodium formaldehyde 
sulphoxalate, which is designed to overcome a certain difficulty in 
administration of the salvarsan, due to acidity of its solutions. 

Ehrlich assumes that the parasite of syphilis, the spirochete, 
possesses among others, arsenio-receptors, and that through the 
combination with this arsenic compound the parasite is poisoned and 
dies. Ehrlich claims that in more than twelve thousand cases in 
which this drug has been administered by him, no single case of 
poisoning has resulted. The administration of the drug, which is 
intravenous, or intramuscular, requires, however, considerable skill 
and care. The treatment with salvarsan is often combined with 
that of mercury. There seems to be no doubt that this preparation 
exerts a specific and destructive action upon the spirochete, and has 
already resulted in the alleviation of an enormous amount of suf- 
fering (often hereditary and undeserved) from this dreadful 
scourge. It is still too early to make final statements as to the per- 
manence of the cures affected although there is much reason for 
hopefulness. It should, however, be noted that this chemothera- 
peutic treatment, unlike the anti-toxin treatment for certain other 
diseases, does not at all produce immunity from later infection from 
the same disease. Indeed, there is some evidence to show that cases 
of re-infection are distinctly harder to treat successfully than those 
of initial infection. The cure of advanced cases of the disease natu- 
rally, presents greater difficulties, because of secondary disturbances 
of the vital organs, but many of these have been materially alleviated. 



30 Ehrlich's Chemotherapy. { A j J^y', m™' 

The progress made in the chemotherapeutic treatment of diseases 
produced by other trypanosomes, notably that of the " sleeping sick- 
ness," has been less marked up to the present. Something has been 
gained, but no specific drug comparable with salvarsan in its effi- 
ciency has yet been found. 

It is, however, recorded that in Surinam a hospital was estab- 
lished to treat cases of another tropical disease known as the yaws. 
In the course of eight days three hundred and twenty-eight cases 
were admitted, and at the end of fourteen days the last patient was 
discharged, cured, and the hospital had to be closed. 

In another field the work of Ehrlich has led to procedures which 
are of the greatest promise in the study of the processes involved 
in the progress of medical and physiological research, namely, so- 
called " vital staining." By means of the injection of dye-stuffs into 
living organisms, it is possible, because of the selective receptivity 
of certain tissues or parasites, for a particular color, to trace the 
movement of bacilli, and to watch the changes which they occasion 
in the living organism itself. The same procedure is employed in 
the study of healthy tissue. 

To Ehrlich's clear, analytical mind, exceptional executive ability, 
fine technique, and extraordinary industry is due not only the pro- 
cedure by which certain particular diseases may be arrested, but a 
splendid example of logical attack upon other similar problems, 
which offers great promise for the future, even though, as in the case 
of the anti-toxins, one marked success may not be at once followed 
by others of equal moment. He has demonstrated, in a way which 
cannot be detailed in the scope of this article, that the test-tube ex- 
periments made in the laboratory with a particular drug upon a 
special parasite cannot be alone relied upon as an index of the effect 
upon it of the same drug when it is harbored by the living organism, 
since the action is essentially modified by that organism, and he has 
advanced theories which at least help in the understanding of the 
possible reasons for the variations in behavior thus observed. Even 
though Ehrlich's chemotherapy may not be, in an exact sense, a " new 
science," it must be acknowledged to be a most fruitful and helpful 
combination of the principles of two well-recognized and time- 
honored sciences for the benefit of mankind. 



Am. Jour. Pharm. ) 
January, 1914. J 



Oil of Sandalwood. 



3i 



OIL OF SANDALWOOD. 1 

By E. M. Holmes. 

The gradual, but steady, increase in the price of sandalwood 
oil during the last few years has naturally given rise to enquiries 
concerning its cause. Neither the growing use of the oil for 
medicinal purposes, nor the large demand for the wood in India 
and China, can sufficiently account for it. There is, however, 
a possible cause that has apparently not received the attention it 
deserves from merchants in this country. During the last 30 years 
or more, Lantana and Casuarina plants have been introduced into 
sandalwood plantations with the idea of their shade helping the 
growth of the young sandal plants, and it appears that concurrently 
with a diseased state of the Lantana, the sandal plants have become 
affected with what is known as the spike disease. 

A most interesting account of this disease is given by Mr. F. S. 
Mason in the Pharmaceutical Journal in 1903 (May 30th, p. 756), 
which gives an excellent idea of the character of the disease, and 
of the extent to which the plantations are affected. One remark 
in this paper is well worthy of notice, viz., that " within five years 
it has swept whole tracts of country, and unless some means can be 
devised to check its ravages, it is only a question of time for the 
plant to become very rare, if not extinct." So convinced was the 
Mysore Government of the importance of rinding a means to check 
the disease, that in 1907 the Maharajah of Mysore offered a prize 
of 10,000 rupees to anyone who could discover the cause of the 
disease, and devise a curative treatment for it. But although the 
offer remained open until 19 10 no one succeeded in winning the 
prize. 

The cause of the disease was investigated on behalf of the 
Indian Government by Mr. Barber and Dr. Butler, and they came 
to the conclusion that it was not due to any animal or vegetable 
parasite, but was connected with the disc-like suckers at the ex- 
tremities of the roots of the sandalwood tree, by which it attaches 
itself to the roots of other plants and obtains nourishment from 
them (Indian Forester, xxxiii, 1907, p. 199). That no curative 
means of arresting the disease has yet been devised is evident from 



^he Perfumery and Essential Oil Record, June, 1913, 161. 



Oil of Sandalwood. 



Am. Jour. Pharm. 
January, 1914. 



a statement published last October in the same journal, to the 
effect that the disease still continues with dire results, and that 
in two districts alone some 70,000 sandal trees had to be uprooted. 

In order to obtain an idea of the probable cause of this disease 
it is necessary to pay some attention to the life history of the plant, 
so far as this is known. As already mentioned, the sandal tree 
is a root parasite, obtaining its food by means of suckers, which it 
attaches to the roots of other trees. It has been ascertained by 
Rama Rao that there are at least 144 species of plants which the 
sandal tree attacks in this way, as proved by experiment with sandal- 
wood seedlings, and he gives a list of 252 plants which are found 
growing near or with the sandal tree, but are as yet not known to be 
utilized as a source of food by this tree. It does not appear to be 
equally nourished by all of its host plants, and the condition of the 
tree depends upon the vigorous and healthy state of its host. Thus 
it is known that a plant on which it will thrive in one district fails 
to keep it in a healthy state in another, where the conditions are 
unsuitable to the healthy growth of the host plant. This require- 
ment of the sandalwood tree is well shown by an observation 
recorded in the Indian Forester, (xxxl, p. 191), that when a trunk 
of Heptapleurum was cut down, the sandal plant attached to its 
roots began to wither, but when new shoots formed on it the sandal 
plant began to revive. The sandalwood tree sends out roots for 
150 feet or more, and therefore requires a comparatively loose 
and well-drained soil which the roots can easily penetrate and 
spread in. In a natural state it flourishes at an altitude of 1500 
to 4000 ft., the best yield of oil being obtained from trees growing 
between 2000 to 3500 ft., on loose volcanic soil mixed with rocks, 
and preferably ferruginous in character. It requires to be shaded 
by thickets above which it can form a head of leafy branches. 

Although in rich soil it grows more luxuriantly, less scented 
wood is formed, although, as the tree furnishes more wood, the 
proportion is about the same. It is considered that the richness of 
the wood in oil depends more upon elevation and exposure, since, 
although the tree grows luxuriantly at 700 ft., the wood is said to be 
totally devoid of scent at that altitude (Indian Forester, xxvl, 
pp. 1-50, 1900). 

The experiments made by Rama Rao indicate that the physical 
conditions of soil and drainage affect the development of the root- 
branching system. The soil needs to be well drained, as the seed 



Am. Jour. Pharm. \ 
January, 1914. j 



Oil of Sandalwood. 



33 



rots in soil where stagnant water is present, more readily than in 
most plants. 

The seed of the sandalwood tree germinates freely in the thickets 
where the tree grows, within a month of being sown, although 
germination may occur any time during three months or longer, 
but if the seed germinates in open ground where it does not meet 
with other roots, the seedlings soon wither and die. The young 
plants for plantations must therefore be raised by planting them 
with other plants on whose roots the seedlings can feed as soon 
as they have exhausted the nourishment of their own seed lobes, 
which lasts for about two months. The seeds are therefore planted 
in short wide tile tubes resembling drain pipes, but shorter, so that 
the young seedlings can be planted out without disturbing their 
root attachments. This planting out is done when they are about 
4 ins. high or rather more than a year old. If allowed to grow 
larger there is likely to be injury done to the roots in planting them 
out. After planting out, the seedlings require to be gently but 
copiously watered until well established. 

Experiment has shown that the best plants to grow with the 
seedlings are Pongamia glabra, Gossypium arboreum, Albizzia, Leb- 
bek and Cleistanthus collinus. 

The seedlings need protection from animals, as the foliage of the 
sandalwood plants proves very attractive to them. Cattle and goats 
will greedily eat the foliage whenever they see it, and deer will 
leap over the obstructing bushes to get at it, and hares will creep 
through the thicket to reach it. 

As the seedlings in a wild state reach only a height of 3 ins. 
the first year, and 12 ins. the second year, they are easily destroyed. 
It is only in the fifth or sixth year they appear above the surround- 
ing bushes and form a leafy head. At this time the stem is about 
1 in. in diameter. 

It takes 18 to 25 years before the tree is fit to yield oil. With 
respect to the spike disease, the trees attacked by it present the 
appearance of being dead, but on careful examination many leaves 
are seen to be scattered over the tree at the end of the stiff branches, 
but they are very small, and form small terminal tufts, hence the 
name " Spike " disease. The shoots are found to be full of starch, 
indicating that the plant has not been able to utilize its stored-up 
nourishment. The disease is pronounced to be infectious, because 



34 



Oil of Sandalwood. 



(Am. Jour. Pharm. 
\ January, 1914. 



all sandal plants, in plantations where it occurs, have died, whilst 
solitary trees are still thriving. 

From the above facts, recorded by various observers, it becomes 
evident that the sandalwood tree requires plenty of room so as to 
be able to select vigorous hosts to feed it; that it requires soil por- 
ous enough to enable its roots to spread readily, and that, therefore, 
if too closely planted, it may easily be starved, especially in hard or 
heavy soil. The fact that isolated trees thrive in a natural condition 
also indicates that the disease is one of mal-nutrition, whilst the 
presence of starch in the withered shoots indicates the absence of 
a suitable enzyme to transform it into soluble food. 

Apparently no attempts have as yet been made to ascertain the 
chemical constituents that the tree contains, and therefore needs, 
although Peterson (Pharmaceutical Journal (3), xvl, page 575) 
found that Macassar sandalwood was rich in iron (7.5 pc) and 
contained traces of manganese. The latter metal is believed to be 
connected with the activity of enzymes, and it is possible that a 
deficiency of it in the soil may injuriously affect the growth. Re- 
search is also evidently necessary to ascertain if the tree selects one 
ingredient for its nourishment from one tree and other ingredients 
from other species, as it is well known that certain enzymes can 
split up other bodies than those on which they usually act. 

There is evidently much to be done before the cause of the 
disease and the means to prevent it can be ascertained. 

Regarding the subject from the commercial side, the possibility 
of other sources of sandalwood suggests itself. The world's supply 
of sandalwood oil is at the present time chiefly derived from the 
trees grown in Southern India, only a comparatively small quantity 
coming from the Islands of Timor and Sumba via Macassar. The 
yield from Mysore last year was 2469 tons of sandalwood, exclusive 
of chips and sawdust. The average price, including chips and saw- 
dust, was 471 rupees as against 461 rupees per ton during the 
previous decennial period. 

The only other oil that at present competes with the East Indian 
sandalwood oil is that of Amyris balsamifera L., a tree belonging 
to the natural order Burseracese, the wood of which is imported 
from Venezuela, and is known in Europe as West Indian sandal- 
wood. It competes, however, only in medicinal use, not in per- 
fumery. 

Of the 20 or more known species of Santalum, which are dis- 



Am. Jour. Pharm. \ 
January, 1914. j 



Oil of Sandalwood. 



35 



tributed over Asia, Australia, New Caledonia and Polynesia, several 
were rendered almost extinct by the ruthless destruction of the 
trees during the first half of the last century, and are not now 
available in quantity for commercial purposes. These include 
5\ Freycinetianum, Gaud., of the Sandwich Islands, S. Hornet, 
Seem., of Eromanga, S. insular e, Bert., of the Marquesas and Do- 
ciety Islands, and 5\ Yasi, Seem., of the Tongo Islands, and 5. Aus- 
tro-Caledonicum, VieilL, of New Caledonia. The wood of these 
trees was chiefly collected for the Chinese market, and not for the 
distillation of oil. None of these trees, so far as is known, yields 
an oil equal in fragrance to that of 5". album. 

A log of wood of Santalum Yasi from the Indian and Colonial 
Exhibition was distilled by Mr. C. Umney in 1886, and a sample of 
the oil sent to Messrs. Schimmel and Co., who considered it in- 
ferior both in perfume and therapeutical effect to that of Santalum 
album. The yield appeared to be 6y 2 per cent., although the real 
percentage might have been less, as an unusual amount of water 
separated from the oil in the winter weather. 

Of the trees yielding sandalwood in Australia, some of which 
were formerly classed in the genus Santalum, the oils are known 
only in a few cases. That of Fusanus spicatus R. Br. (formerly 
Santalum cygnorum) or West Australian sandalwood oil, is dis- 
tilled to some extent in West Australia, but is considered by 
Gildemeister and Hoffmann to have an unpleasant resinous odor, 
and not fit to be used as a substitute for East Indian sandalwood oil. 
It is, however, the nearest to the true sandalwood oil, and contains 
75 per cent, of alcohols, which have, however, not been positively 
identified with santalol, but owing to the small yield of oil (2 per 
cent.) and the expense of labor in Australia, although the tree 
is fairly plentiful, it cannot compete with the Indian oil. That of 
F. acuminatus R. Br. (formerly Santalum Preissianum Miq.) 
known as South Australian sandalwood, yields a vivid cherry-red 
oil, from which crystals separate out on cooling. It has a different, 
somewhat rose-like odor, and a different composition and specific 
gravity to that of East Indian sandalwood. Exocarpus latifolius 
R. Br., a West Australian plant, may perhaps yield some of the 
West Australian sandalwood oil, but there is no evidence that it 
yields an oil resembling that of true sandalwood. 

Several fragrant woods are known under the name of sandal- 
wood in other countries; the wood of Osyris tenuifolia, Engl., a 



36 



Oil of Sandalwood. 



{Am. Jour. Pharm. 
January, 1914. 



native of Kilmandscharo, in East Africa, has been imported into 
Germany under the name of East African sandalwood. The oil 
was described in 1908 as being bright brown in color with an odor 
intermediate between that of vetivert and gurjun balsam, but quite 
different from sandalwood (Pflanzenweldt Ost. Afrika C. 167, 
Schimmel's Report, November, 1908, p. 109). 

The Madagascar " Sandalwood," of which the native name is 
apparently " Hasoranto," is exported from Tamatave in the North 
of Madagascar to Zanzibar, and thence to Bombay, where it is 
known as taggar wood, and is largely used as a cheap substitute for 
sandalwood for funeral pyres. The wood is of a dark brown 
color, and yields a dark-colored thick oil, with an odor slightly 
resembling sandalwood, but which for medicinal or perfumery 
purposes could by no means be used as a substitute for it. Its 
botanical source is unknown, but is supposed to be a Lauraceous 
tree. 

New Zealand Sandalwood. — The wood of Olearia Traversii, 
F. Muell, was exhibited at the International Exhibition in 1886 
under the name of bastard sandalwood. It belongs to the Family 
of Compositae, but nothing appears to be known of its oil. 

Cochin China Sandalwood. — This is ascribed by Baillon to 
Epicharis Loureirii, Pierre, Fam. Melacese, but I have not seen a 
specimen. 

Guiana Sandalwood. — The oil has already been described 
(P. & E. O. R., 191 1, p. 79). Dr. Giessler, of Leipzig, is of opinion 
that the oil is probably derived from three species of the genus 
Acrodiclidium, or Ocotea (Schimmel's Report, October, 191 1, 
p. 82). It does not resemble sandalwood oil in odor and is not 
known to do so therapeutically. 

Ibean Sandalwood. — The wood of Brachylana Hutchinsii, 
Hutchinson (Family Composite), is known under this name. 
The tree grows near Nhairobi and in forests near the coast at an 
elevation of 5000 to 6000 feet. The timber is white, hard, easily 
worked, and scented when freshly cut, and is not subject to the 
attacks of white ants. The native name of the tree is " Muhugu." 
It does not appear to have been exported as yet, the tree being only 
described three years ago in the Kew Bulletin, 1910, p. 126. The 
plant is illustrated in the Icones Plantarum, 292a. 

It is obvious, therefore, that at present there is no oil known 
that can altogether take the place of sandalwood oil, and until a 



A jan J uTry, P i9i4 m *} Pa - State Pharmaceutical Association. 37 

means of combating the spike disease has been discovered and the 
best method of cultivation of the tree has been ascertained, the 
price of sandalwood is likely to rise, especially since it takes from 
18 to 25 years for the tree to arrive at maturity and to grow 
scented wood. 

The chemical constitution of the oil does not hold out much 
hope that it will be an easy matter to produce it synthetically, for 
even if santalol can be produced from piperidine, there are evidently 
other constituents that go to form the odor of the oil, and unless 
these can be ascertained it is not likely to take the same place 
in perfumery or medicine as the oil distilled from Santalum album. 



ABSTRACTS OF SOME PAPERS READ AT THE 1913 
MEETING OF THE PENNSYLVANIA STATE 
PHARMACEUTICAL ASSOCIATION. 

By John K. Thum, Ph.G., Philadelphia, Pa. 

What is the Quality of Pancreatin on the Market? 

By Charles H. La Wall. 

An examination of some pancreiatin by the author disclosed the 
interesting fact that it was adulterated with powdered malt. Of 
course this raised the starch converting power, and, as the author 
states, as this test is the only one applied sometimes and as the 
general appearance of such a sophisticated sample is normal, a more 
than superficial examination of pancreiatin is necessary to insure 
good quality. 

Sterilization in Pharmacy. 

By A. Parker Hitchens, M.D. 

The author in a very interesting and illuminative manner de- 
scribes the possible purposes of sterlization in pharmacy and gives 
in detail the various methods which have been found to* be of value. 

Crotalin — Collection, Preservation, Chemistry and Action. 
By Walter Roth well. 

Attenuated snake venom, obtained from Crotalus Horridus, 
commonly known as " rattlesnake," has obtained some vogue in 
recent years in the treatment of epilepsy. The author briefly de- 



38 Pa, State Pharmaceutical Association. { A j an J u ° a ^; ^In- 

scribes the method of obtaining the venom, its preservation, chemis- 
try, and action. It is given hypodermatically and its action is to 
increase the time of the coagulation of the blood. 

The Detection of Cane Sugar in Honey. 

By Charles LaWall, Ph.M. 

The author concludes that it is impossible to detect added cane 
sugar in honey by means of a qualitative test ; being present normally 
in small amounts its quanitative determination is preferably accom- 
plished by means of the polariscope. Invert sugar is the kind 
usually added and dan be easily detected in honey that has never 
been heated. 

Oregon and Canada Balsam of Fir. 

By J. G. Roberts and M. M. Becker. 

The writers state that because of the scarcity of Canada Balsam 
of Fir for the last year or two a suitable substitute is desirable. 
And as a substitute Oregon Balsam of Fir is offered to the trade. 
As is well known this product closely resembles Canada Balsam of 
Fir. 

Finding that the literature on Oregon Balsam contained little 
information the authors obtained some balsam from a known source 
and endeavored to obtain data as to tests for identity and purity. 

It differed in the main from Canada Balsam in viscosity, solu- 
bility in alcohol, and in response to the magnesium oxide test. The 
Oregon Balsam is thinner; it is completely soluble in alcohol in 
contradistinction to the official balsam which yields a turbid solu- 
tion. Canada Balsam when mixed with 20 per cent, of its weight 
of magnesium oxide previously moistened with water, becomes 
solid. The Oregon does not solidify even when mixed with 60 per 
cent, of its weight of magnesium oxide. It was also noticed that 
the Oregon Balsam does not dry as readily as the Canada Balsam, 
a quality which renders it inferior to the latter for microscopical 
work. 

Socotrine Aloes. 

By C. J. Denneby. 

The author remarks that although the United States Pharma- 
copoeia definition of aloes is broad enough to allow recognition of 
all varieties of genuine aloes yet it neglects to describe some samples 



Am. Jour. Pharm. \ 
January, 1914. / 



Book Reviews. 



39 



as imported. It is often received in barrels in a pasty condition, 
containing nearly twice the amount of water permitted by the 
U. S. P. It is further remarked by the author that when in this 
condition the only recourse is rejection of the shipment as abnormal 
as to its physical appearance, or, it being satisfactory as to identity 
and purity, to dry so that sample is of proper U. S. P. quality. A 
tabulation of five samples is given ; all contained twice the quantity 
of water allowable ; they also failed to pass the alcohol test for 
limit of gums, dextrins and impurities. While Kraemer and others 
state that aloes should not yield more than 4 per cent, of ash all of 
these samples were slightly higher. As is well known and has been 
for some time, no aloes is obtained from Soeotra. 

The Microscopic Examination of Ointments. 

By Fritz Heidlberg and Chas. E. Vanderkleed. 

The value of an ointment, the authors state, consists mainly in 
the fineness or subdivision of the active ingredient suspended in 
the vehicle. And to properly determine when the ointment has 
been manipulated long enough for the active ingredient to be uni- 
formly and evenly divided they advise the use of the microscope. 
They state that this is the only satisfactory way to tell whether 
uniform results have been obtained. They also give their technic 
for preparing slides for this purpose and illustrate by showing 
micro-pho'togriaphs of mercury ointments. 



BOOK REVIEWS. 

Digest of Comments on the Pharmacopoeia of the United 
States of America (8th Decennial Revision) and on the 
National Formulary (3RD Edition) for the Calendar Year 
Ending December 31, 191 i. By Murray Gait Motter and Martin 
I. Wilbert. 

The foregoing title, known also as Bulletin No. 87, Hygienic 
Laboratory, needs little introduction to the progressive members 
of the pharmaceutical profession. It speaks for itself. It is suffi- 
cient to say that the literature covered in this review embraces 
matters that must, if thoroughly and painstakingly studied by the 



40 



Book Reviews. 



( Am. Jour. Pharm. 
\ January, 1914. 



two revision committees, result in the publication of a Pharmaco- 
poeia and National Formulary that will be regarded as authoritative 
and the last word in pharmaceutical matters. 

References to the great mass of literature consulted is com- 
plete in every respect and comments relating to the legal status and 
development of pure food and drug laws, scope, analytical data, 
clinical tests, biologic products and vegetable drugs are abstracted 
with the main points of the papers brought out. This is as it should 
be, as it enables a worker to see at once if a reference is worth while 
consulting. 

It is particularly gratifying to note that references of a practical 
nature in regard to pharmaceutical preparations and suggestions as 
to their improvement, both as to formula and method of prepara- 
tion, are much in evidence. 

The " digest " also places at the disposal of the revision com- 
mittees references to all literature pertaining to international 
standards. Every decade brings us closer to a realization of the 
fact that the question of unification of pharmacopceial preparations 
is becoming a matter of supreme importance. Rapid means of travel 
and communication are largely responsible for this. 

Foreign Pharmacopoeias always bring forth considerable comment 
and criticism from workers and experts from various parts of the 
globe and last year was no exception. The collaborators of the 
" Digest " make this fact plain in their references to literature that 
comments on the German, Russian, Italian, French, Swedish, Swiss, 
Austrian, Japanese, Dutch, and British Pharmacopoeias and the 
British Pharmaceutical Codex. 

Part III of this Bulletin is devoted to a most comprehensive 
review of the literature relating to> comments on official articles 
504 pages being required to show what has been said and done in 
this field of endeavor, and also illustrating what a tremendous 
amount of reading the preparation of this valuable government 
publication required for its completion. 

John K. Thum. 

The Propaganda for Reform in Proprietary Medicines. 
Reprinted from the Journal of the American Medical Association. 
Eighth Edition, 1913. 

There are many people who take as gospel truth anything they 
see in print. There are a great many other people who, while they 



Am. Jour. Pharm. ) 
January, 1914. J 



Book Reviews. 



41 



know better than to do this, are unable to discriminate and so are 
almost as easily led as the others. Then there are many people 
afflicted with some ailment, or think that they are, who clutch, like 
a drowning man after a straw, any statement which seems to bear 
upon their case. 

To satisfy the " needs " of people like these there is a host of 
firms who manufacture remedies for every conceivable trouble, and to 
eliminate the need of having a physician they include in their packages 
circulars which purport to give complete directions of use. So 
extraordinary are some of these statements that anyone even only 
very superficially acquainted with the facts would prick up his ears 
at hearing them. But not so with the gullible public. The more 
extreme the statement, the more absolute dependence they place on 
the product. 

Truly, this proprietary medicine venture is no more than a 
psychological game between the manufacturer and the public, only 
the public is not aware that it is playing the game. Here are some 
of the psychological weapons the manufacturer has at his command : 

1. As one bows down to a man who is well dressed and imposing 
in appearance, so one worships an ordinary drug or food (or even a 
worthless one) when it is clothed in a dignified name. 

2. As the average illogical mind believes that what comes after 
must be due to what goes before, the deduction is easily made that 
if a person recovers after having made use of some remedy, the 
remedy deserves the credit. This is termed the post hoc, ergo propter 
hoc argument. The folly of course lies in the fact that in the great 
percentage of cases the patient would have recovered without any 
remedy. 

Yes, the Propaganda for Reform in Proprietary Medicines, which 
is a bound volume of reprints, might well be called " A Study in 
the Psychology of Advertising Worthless Products." A former 
book of reprints entitled " Nostrums and Quackery " is relative 
especially to those nostrums which are exploited only — or chiefly — 
to the public. The volume under consideration, however, relates to 
those products which are exploited to the physician and includes 
also some of those in the other -volume where there seemed to be an 
" overlapping." 

Some 120 proprietaries are considered, the schemes by which 
they are foisted upon the public through the medical profession are 
discussed with numerous reproductions of illustrations of advertise- 



4 2 



Book Reviews. 



{Am. Jour. Pharm. 
January, 1914. 



ments, and chemical formulas and therapeutic properties are given. 

A striking feature is the prominence which must be taken by 
the products of large well-known manufacturing houses who are 
making a mighty good thing out of the credulity of the public with 
no regard to the ethics of the profession. 

A. K. Lobeck. 

ARBEITEN AUS DEM Ph ARM AZEUTISCHEN INSTITUT DER UnIVER- 

sitat Berlin, by H. Thorns, v. 10, including the work of the year 
191 2, Urban & Schwarzenberg, Berlin, Wien, 191 3, 220 pages, with 
two illustrations. 

This volume like the ones preceding it reflects the work done in 
the Pharmaceutical Institute of the University of Berlin, by Prof. 
Thorns and his associates, and includes a total of 35 contributions, 
under five general headings: 1, Contributions from the division for 
the examination of drugs, specialties and secret remedies ; 2, reports 
on organic chemical work ; 3, microchemical work ; 4, reports from 
the division for the examination of foods and technical products of 
the Colonies ; 5, general discussion. The whole is followed by an 
index of four double column pages. The first section of the book 
includes a systematic review of the new remedies introduced during 
the year 191 2, and reports the analytical examination of a number 
of proprietary preparations. The phytochemical work reported in 
this volume includes observations on the production of menthol in 
Germany and in the German Colonies, and an examination of the 
seed of Strychnos kongofera for strychnine. Lenz discusses the pro- 
duction and use of microchemical reagents in a paper covering eight 
pages, and Thorns, in a very comprehensive paper, reviews the 
problems of pharmaceutical education in Germany and other 
European countries. 

Altogether the volume is well up to the high standard that has 
been established by those preceding it and the renewed energy with 
which the work on so-called new remedies is being prosecuted bodes 
well for the general progress of pharmacy along satisfactory lines. 

M. I. W. 

ARBEITEN AUS DEM Ph ARM AZEUTISCHEN INSTITUT DER UNIVER- 

sitat Berlin, herausgegeben von, Prof. Dr. H. Thorns. 

This publication, the tenth annual volume, consisting of 220 
pages, presents a record of the work accomplished during 1912 at 



Am. Jour. Pharm. 1 
January, 1914. j 



Book Reviews 



43 



the Pharmaceutical Institute of the University of Berlin under the 
direction of Dr. H. Thorns, the Director. 

It also gives evidence that the German pharmacist, acting 
through this pharmaceutical institute, is alive to the need of pro- 
tecting the medical profession and the public against fraud, secret 
medicines and mendacious advertising. Here, in our own country, 
the pharmacists have been so busy worrying about price protection 
on nostrums and telephone rates that the medical profession took the 
bull by the horns, so to speak, and through its national organization, 
the American Medical Association, organized a permanent com- 
mittee, and named it the Council on Pharmacy and Chemistry. 
What this council has done since its organization is known to a 1 l 
progressive pharmacists. And its efforts for better things are surely 
showing results. One has but to glance over the proceedings and 
reports of some of the medical and pharmaceutical societies to realize 
that we are at the dawn of a new era as to things pertaining to 
these two professions. 

The investigations of the laboratory workers of this German 
institution covered a wide field in the domain of synthetic chemistry, 
particularly as regards the output of the dye houses of that country, 
specialties of all kinds, and secret remedies and nostrums of all 
kinds. 

Under the classification of Analgesics, Antipyretics, and Anti- 
rheumatics, considerable attention is given to such chemicals as 
Melubrin, one of the more recent antipyretics, said to be useful in 
rheumatism and resembling in its effects the salicylates, chemically 
it is sodium-phenyl-dimethyl-pyrazolon-amido-methan-sulphonate ; 
Atophan, said to be useful as an antirheumatic in so far as it aids in 
the elimination of uric acid and chemically known as phenyl-quinolin- 
carboxylic acid ; Novatophan a modification of atophan and taste- 
less while the latter is bitter ; Aspirin Soluble which is the calcium 
salt of acetyl-salicylic acid ; Luminal, a sedative and hypnotic, the 
chemical name of which is phenylethylmalonylurea ; Brophenin, a 
combination of bromine with phenetidin and chemically known as 
bromisovalerylamino-acetate-p-phenetidin ; many others too numer- 
ous to mention are also considered. 

Besides giving considerable space in this publication to the in- 
vestigation of products (Kolonialprodukte) from the German 
colonies, both as to their chemistry and pharmacognosy, there also 
appears an exposure of some of the nostrum emmenagogues found 



44 



Book Reviezvs. 



i Am. Jour. Pharm. 
I January, 1914. 



on the German market. One of these consisted of small quantities 
of oil of cinnamon and cloves in 12 per cent, of alcohol. For two 
ounces of this wonderful and efficient (?) preparation the modest 
sum of one dollar was asked. Another, called " Menstruationpulver " 
consisted of a very poor quality of powdered Roman Chamomile, 
and for the small (?) sum of seventy-five cents the buyer received a 
package containing 35 grammes. 

An interesting report is given of an examination of a fixed oil 
sent to the Institute by a German missionary pastor from Venezuela. 
This oil is used by the Indians in the region of Orinoco as a remedy 
in the treatment of tuberculosis. The results are reported as good. 
This oil is yellow in color, slightly cloudy, and in odor and taste 
somewhat resembling olive oil ; at room temperature fluid ; on cool- 
ing there was separated a small mass of fatty acid which, on warm- 
ing, disappeared. At 12 C. the oil congealed to a soft butter-like 
mass. It was miscible in all proportions with ether, chloroform, 
petroleum benzine, benzol, and carbon disulphide and on the con- 
trary immiscible with absolute alcohol and glacial acetic acid. On 
the addition of HC1 and furfurol no red coloration appeared. The 
test for cotton-seed oil by the addition of sulphur and carbon disul- 
phide gave negative results. The constants were ascertained in the 
usual manner and found as follows : 



Specific gravity at 15 C 0.9125 

Acid number 4.46 

Saponification value 200.45 

Iodine value according to Hiibl after 2 hours 69.9 

Iodine value according to Hiibl after 6 hours 71.0 

Unsaponifiable constituents 0.48 per cent. 

Refractometer number in a Zeiss butter-refractometer at 25 . 59-60 

Optical rotation in 200 ccm.-tube o 



The oil also gave the reaction for elaidin. Hehner's method for 
the separation of the fatty acids was used and the melting point of 
these was found to be 30.31 °, the congealing point 22 and the 
saponification value 195.5. The fatty acids also gave an iodine value 
of 75.25. After recrystallization from alcohol twice, the elaidic acid 
showed a melting-point of 51 °. Experiments on mice proved this 
Ceje-Ol, as it is termed, to be non-toxic. Whether it will be of 
any more value than other better-known fatty oils in the treatment 
of tuberculosis remains to be proven clinically. 



Am. Jour. Pbarm. ) 
January, 1914. / 



Book Reviews. 



45 



As one reads through this volume, depicting the work done at 
this institute, the impression is gained that the aim of the workers is 
the scientific one, the desire for the truth; the truth about those 
remedies for which there may be a legitimate use and which are 
more or less ethically introduced, and the exposure of those remedies 
which are secret in composition and for which extravagant claims 
are made. John K. Thum. 

" A Hankbook of Useful Drugs." A selected list of important 
drugs suggested for the use of teachers of materia medica and 
therapeutics and to serve as a basis for the examinations by state 
medical examining and licensing boards. Prepared under the direc- 
tion and supervision of the Council on Pharmacy and Chemistry of 
the American Medical Association. Press of the American Medical 
Association, 535 North Dearborn Street, Chicago, 1913. 

It does not require the gifts of a seer or the abilities of a prophet 
to venture the opinion that this rather diminutive volume of 167 
pages is destined in the near future to have a decidedly far-reaching 
influence on the teaching and on the practice of therapeutics and, 
consequently, is designed to have an equally important bearing on 
the future development of pharmacy and the efficiency of pharma- 
cists generally. 

Conscientious students of medical economics have long appre- 
ciated the waste of energy, money and even life resulting from the 
haphazard or ignorant misuse of drugs and medicines so general a 
decade or more since. Some nine years ago the Council on Phar- 
macy and Chemistry of the American Medical Association made its 
first onslaught on quacks and quackery in the medicine supply busi- 
ness and although the Council at that time had fair reason to be- 
lieve that it might be assisted in its efforts by at least the more 
progressive of professional pharmacists, this expected cooperation 
has not been forthcoming, in this country at least. Medical prac- 
titioners, largely through the American Medical Association, have 
been compelled to stand practically alone in their fight against the 
purely commercial spirit in the practice of pharmacy of to-day. The 
little book before us is the latest step in this warfare, representing as 
it does the fundamentally constructive work of the Council on Phar- 
macy and Chemistry, as the earlier work " Propaganda for Reform " 
represents the destructive work of the same body, and the now well- 
known book, " New and Non-official Remedies " represents a com- 
pilation of reasonably good material that is offered for future in- 



46 



Book Reviews. 



f Am. Jour. Pharm. 
\ January, 1914. 



elusion in the recognized materia medica of conservative medical 
practitioners. 

The object of this, the latest of the three books offered by the 
Council on Pharmacy and Chemistry of the American Medical Asso- 
ciation, is perhaps best shown by quoting rather liberally from the 
preface, not necessarily exactly but rather the purport of the state- 
ments made, so as to avoid occasional repetition : 

" Many of the articles in the Pharmacopoeia and in the National 
Formulary are worthless or superfluous. The repeated efforts that 
have been made to eliminate at least the more useless of these 
articles have uniformly encountered the assertion that the articles 
objected to are used somewhere by some one, and that they should, 
therefore, be officially recognized and authoritatively defined. 

" For a number of years men active in the work of the Council 
on Medical Education and in the Confederation of State Examining 
and Licensing Boards have been trying to restrict instruction and 
examination in materia medica to the more important drugs. These 
efforts apparently failed, so far as the Committee of Revision of the 
U. S. P. is concerned, but the suggestions have been taken up and 
elaborated by the Council on Pharmacy and Chemistry and the result 
is this volume on useful drugs. 

" The book is offered as a fundamental list of drugs and prepara- 
tions with which all medical students and practitioners might be 
expected to be familiar, and to which, therefore, state examining and 
licensing boards might largely or entirely confine their examinations 
in materia medica. As it now stands, it embodies a total of about 
455 headings including 265 titles of drugs and chemicals, 137 phar- 
maceutical preparations, 13 cross references and 40 general defi- 
nitions or descriptions of forms of medicines." 

It is confidently predicted that an intelligent and critical use of 
these selected drugs will prove their general sufficiency, and show 
definitely that many drugs now discussed in text books and official- 
ized in pharmacopoeias, are, to say the least, superfluous. A careful 
study of this book is also well designed to demonstrate that many 
newly discovered or widely exploited proprietary preparations have 
no appreciable advantage over established drugs and preparations 
whose limitations and possible untoward results are generally well 
known. 

Pharmacists and teachers of pharmacy should acquaint them- 
selves with the nature as well as the intent of the volume. The last 
word on a limited list of useful drugs has not as yet been said, but 



Am. Jour. Pharm. \ 
January, 1914. / 



Book Reviews. 



47 



the agitation will undoubtedly do much toward insuring a more 
uniform and better supply of recognized, standard drugs, by placing 
responsibility for the identity and purity of drugs and preparations 
on the dispensing pharmacist, where it rightly belongs. By ulti- 
mately restricting the number of drugs and preparations used it 
will be possible to provide adequate supervision of the medicines dis- 
pensed ; and thus the pharmacist will eventually come to occupy the 
place he rightly deserves as an important factor in safeguarding 
public health. M. I. W. 

War Department: Office of the Surgeon General, Bulletin 
No. 3. Studies of Syphilis. By Charles F. Craig, Captain, Medical 
Corps, U. S. Army, and Henry J. Nichols, Captain, Medical Corps, 
U. S. Army, with introduction by Major Frederick F. Russell, 
Medical Corps, U. S. Army. 

This Bulletin, published for the information of medical officers 
by authority of the act of Congress approved August 23, 191 2, and 
with the approval of the Secretary of War, is striking evidence of 
the fact that the wonderful advances made in the last decade for the 
diagnosis and treatment of syphilis are being made use of and appre- 
ciated by the medical men of the army. In no branch of medicine 
has more rapid progress been made. And, as pointed out in the 
introduction, " it is noteworthy that medicine is indebted to* lab- 
. oratory workers and research institutions, and not to the practical 
syphilographers, for this phenomenal progress." 

Exclusive of the introduction the Bulletin consists of a series of 
seven papers commencing with a study of the Spirochceta pallida, 
its morphology and cultivation. Under the head of immunity the 
interesting statement is brought out that there is no true immunity 
following an infection from this parasite. A person once infected 
and cured can be reinfected. Opinions contrary to this were long 
held by the medical profession. 

The diagnosis of syphilis by the complement fixation test, or 
Wassermann test, as it is more generally known, is gone into very 
fully. That this test has proven of great value in .the army for 
diagnosis and control over treatment is attested by the experience 
gained from the performance of 12,000 reactions. 

Ehrlich's great discovery, salvarsan and neosalvarsan, naturally, 
have been used and the behavior of these arsenic combinations with 
the benzol ring, in the treatment of syphilis is very fully gone into. 
The superiority of these drugs over mercury as a specific is clearly 



48 



Book Reviews. 



iAm. Jour. Pharm. 
January, 1914. 



proven; yet, in the light of our present knowledge, the consensus 
of opinion is that a wise combination of mercury plus salvarsan or 
neosalvarsan intravenously procures the best results. 

The work recorded in this Bulletin clearly emphasizes the fact 
that the Medical Corps of the Army, in its care of our fighting men, 
possesses unusual facilities for the scientific observation, study, and 
treatment of .this disease. John K. Thum. 

Essentials of Prescription Writing. By Cary Eggleston, 
M.D., Instructor in Pharmacology, Cornell University Medical 
College, New York City. W. B. Saunders Company, Philadelphia 
and London. 

Within the confines of this small volume which consists of only 
115 pages, a medical student or graduate physician may find all 
the information necessary to equip himself in the principles of 
prescription writing, a branch of medicine in which most graduates 
in medicine find themselves utterly at sea when first starting prac- 
tice. Some overcome this handicap and some do not; to the latter 
we most heartily recommend this handy little book, although, as a 
matter of fact, it may be read with profit by all who practise 
medicine. 

This book consists of ten chapters which embody the funda- 
mentals in a sequential manner ; the chapter devoted to Latin gram- 
mar is brief but thorough — the author has evidently learned the art 
of saying much in few words — while the suggestions offered as to 
flavoring, coloring, and vehicles (aqueous, hydro-alcoholic and alco- 
holic), if carefully studied and faithfully carried out by physicians, 
would soon result in diminishing, if not abolishing, the proprietary 
medicine evil. John K. Thum. 

Genealogy of the Descendants of Thomas French, with 
Some Account of Colonial Manners and Doings, together with One 
Hundred and Fifty Picture Prints Compiled and Published by 
Howard Barclay French, of the Seventh Generation. Vol. II, Phila- 
delphia. Privately printed, 1913. 

Oliver Wendell Holmes once wrote that " Philadelphia was the 
center of genealogy." With this new contribution which is now 
completed, Dr. Holmes' views are confirmed. A very extended re- 
view of the first volume was given in this Journal in June, 1909, 
p. 309. The work is handsomely gotten out and will stand as a 
monument to Mr. French. 



THE AMERICAN 



JOURNAL OF PHARMACY 



This is an American plant, which has run wild all over India. 
It may easily be known by its glaucous, prickly, thistle-like leaves, 
bright yellow flowers, and milky juice. The latter is used as an 
application to ulcers and in combination with the juice of Aristo- 
lochia bracteata is given internally in syphilis and gonorrhoea. In 
the Concan the juice with milk is given in leprosy. The seeds and 
oil have been used by European physicians. The oil in doses from 
30 to 60 drops is a valuable remedy in dysentery and other affections 
of the internal canal. Fluckiger found 4 to 5 gms. to have a mild 
purgative effect. An extract made from the whole plant has been 
found to have an aperient action and the milky juice to promote the 
healing of indolent ulcers. 

The oil used for examination was obtained by pressing the 
crushed seeds in a screw press in the laboratory in presence of the 
author. The chances of adulteration were thus avoided. 



Some of the crushed seeds were submitted to steam distillation; 
the distillate had a slight opalescence and a very pungent odor, but 
no oil came over. 

47.1176 gms. of the crushed seeds were exhausted in a Soxhlet 
apparatus with petroleum ether, the latter evaporated off when 
10.4966 gms. of a thin brown colored oil was left behind. Hence 
the percentage of oil is 22.3. According to Charbonnier the seeds 
contain 36 per cent, of oil. 

The petroleum ether extract has a pale greenish-yellow color 
with a green fluorescence, if it be evaporated at the ordinary tem- 
perature, the oil left behind has an olive green color. If this be 



THE OIL OF ARGEMOtf E MEXICAN A. 

By Kshitibhushan Bhaduri, M.Sc^ OFFlC^- 



FEBRUARY, 1914 




Historical. 



Experimental. 



(49) 



The Oil of Argemone Mexicana. 



Am. Jour. Pharm. 
February, 1914.. 



either left exposed to the atmosphere or heated on the water bath it 
gradually acquires a rich brown color. If it be still further heated 
the color deepens and it diffuses a very intense odor, like that of 
the juice of the fresh plant. 

The pressed oil was of a deep brown color, had a mild odor and 
was tasteless. The freshly obtained oil was very thin, but on keep- 
ing it gradually thickened. Crossley and Le Sueur (Journ. Soc. 
Chem. Ind. } 1898, 991) say the fresh oil is of orange color and has a 
slight but distinctive smell. 

The mixed fatty acids had a paler color and were very thin. 

The oil on keeping exposed to the atmosphere or on treatment 
with an oxidizing agent deposited a very small quantity of a red 
crystalline substance (M.P. 172 C). 

The oil gradually thickened with the lowering of temperature, 
until at 1 7 C. the clear liquid became turbid, the temperature re- 
mained constant for a little time at 16 C. Charbonnier's oil re- 
mained clear at — 8° C. and Fluckiger's oil at — 6° C. 

The specific gravity was determined at two different temperatures, 
at 28 C. and at the boiling point of water. In the former case it 
was 0.91 17 and at the latter it was 0.9007. Charbonnier obtained a 
specific gravity of 0.920, Fluckiger 0.919 at 16.5 C. and Crossley 
and Le Sueur 0.9247-0.9259 at 1 5.5 C. 

The refractive index obtained with a Pulfrich's refractometer 
was 43 34' at 32 C. or 1.46552. With a butyro refractometer 
Crossley and Le Sueur obtained at 40 C. a refractive index of 62.5. 

The oil and absolute alcohol were miscible in any extent. For 
the determination of its solubility in dilute alcohol the following 
method was adopted. In a stoppered graduated tall cylinder a 
measured volume of oil was introduced, to this a known volume of 
alcohol was added and then water added drop by drop with con- 
tinuous shaking till a permanent turbidity was obtained. The total 
volume was read off and from this when the volume of oil and 
alcohol was subtracted the volume of water added was obtained. 

Table of Solubility in Alcohol of Different Strength at 32°C. 



Oil. 



Water. 



Alcohol. 



10 
10 
IO 
IO 
II 



22 



28 
24 
24 



9 
15 



12 
20 
32 
42 
42 
45 



A Feb£la^ V mT' } The Oil of Argemone Mexicana. 51 

116.4 c.c. oi~ alcoholic potash (calculated) were required for 

the saponification of 3.4828 gms. of oil; hence the saponification 
value is 185.5. The saponification obtained by Crossley and Le Sueur 
is 187.8-190.3. 

The oil was acetylated by boiling with acetic anhydride and 
purified, then dried with anhydrous Sodium Sulphate. 3.23 gms. of 

oil thus obtained required 122 c.c. (calculated) of potash for 

complete saponification. The saponification value of the acetylated 
oil was 213.4 and deducting from this 185.5, the saponification value, 
we got 27.9 as the acetyl value. 

The oil contained a large proportion of free fatty acid for which 
determination 3.5998 gms. of oil was dissolved in 50 c.c. of neutral- 
ized alcohol and a little phenolphthalein solution added and titrated 

with -j^ alkali. It was found that 94.3 c.c. was necessary for 

neutralization, hence the acid value is 146. Two specimens of oil 
were examined by Crossley and Lie Sueur who found 6.0 and 83.9 
as the acid value. 

In the aqueous solution left after the decomposition of the soap 
with an acid, the presence of the following fatty acids was proved 
(1) acetic acid proved by the Cacodyl test and (2) valeric acid by 
the formation of the ester. 

In a weighed flask 2.3696 gms. of oil was taken and dissolved in 
50 c.c. of chloroform, and Bromine gradually added till no further 
absorption took place. It was then evaporated off on the water bath 
and dried. The weight of the brominated oil now was 4.7912 or 
the increase in weight was 102.2 per cent. This is the bromine value. 

The iodine value of the oil is 106.7. That obtained by Crossley 
and Le Sueur is 119,91-122.5. 

2.7 gms. of oil was saponified, then decomposed with dilute 

sulphuric acid and submitted to steam distillation. 0.33 c.c. ©f-^ 

alkali was required for neutralization of 100 c.c. distillate. There- 
fore the Reichert-Meisel value is 0.61. 

From 1.8426 gms. of oil the author obtained 1.7295 gms. of a 
mixture of insoluble fatty acids and unsaponifiable matters. The 
Hehner's value is 94.02. The above authors obtained 95.07. 

The glycerol was estimated by the Benedikt and Zsismondy 
process. This consists in oxidizing the glycerol to oxalic acid by 



52 The Oil of Argemone Mexicana. { A ^b^ary "191?" 

potassium permanganate. From the amount of oxalic acid obtained 
the weight of glycerol was calculated. It was found to be 15.48 
per cent. 

6.1996 gms. of oil was saponified, alcohol evaporated off; it 
was then dissolved in water and extracted with ether. The ethereal 
extract on evaporation left behind .1418 gm. of residue or the oil 
contains 2.29 per cent, of unsaponifiable matter. 

The elaidin produced by the oil was an orange-colored, dough-like 
mass. The reaction was very violent. 

When sulphur chloride was added to a solution of equal volume 
of oil and carbon disulphide a violent reaction ensued, the whole 
mass frothing up; a very sticky mass was left behind. 

When 10 gms. of sulphuric acid was added to 50 gms. of oil the 
rise of temperature was 65 C. The Maumene test was 65 C. 

The rise in temperature on brominating 1 c.c. of oil was 16.5 C. 

The oil gave no characteristic color reaction with sulphuric acid 
even when it was diluted with carbon disulphide. The color was 
blackish-brown in the former case and in the latter case light brown. 

On shaking the oil with nitric acid it acquired a deep brown 
color and the acid a deep red color. On heating it a violent reaction 
ensued, a pale orange-colored scum was formed when the whole was 
allowed to stand over night. 

For the determination of oxygen absorption power a quantity 
of lead was prepared by Livache's method ; about a gram of it was 
spread upon a watch glass and a weighed volume of the oil was 
spread on it by allowing it to drop on different places. This was 
weighed. The weights on each successive day were noted till there 
was no further increase in weight. 



Gain in Weight of 1.3437 gms. of Oil. 



Days. 


Increase in weight. 


Per cent, increase. 


1st day. 


O.269 


2 .002 


2nd day. 


O. 107 


O.8 


3rd day. 


O . OO84 


O.6 


5th day. 


O.OI52 


I . I 


6th day, 


O.OO59 


O.44 


8th day. 


O . OO65 


O.48 


9th day. 


O.OOI5 


O. I 


10th day. 


No increase. 





Total gain in weight till constant = 5.522. 



A reW J uT y) 7oi4 m '} The 0il °f Argemone Mexicana. 53 

39 c.c. of the oil was fractionally distilled at 15 mm. pressure 
when the following fractions were obtained. 



Temperature. 



2i5°-2i7°C. 

2I7°-224° C. 
224°-228° C. 

228°-23I°C. 

23i°-235° C. 



Weight of fraction. 



3-8i 
9.08 
9.24 

6-45 
2.79 



Remarks. 



Instantly solidified. 

Solidified but contained some liquid. 

Liquid, on prolonged keeping a few crystals 

separated out. 
Pale brown liquid. 
Greenish liquid. 



Examination of the Mixed Fatty Acids. 

The specific gravity at 28 C. is 0.9065 and at the boiling point 
of water 0.8889. 

2.0688 gms. required for saponification 90.4 c.c. of alkali. 

The saponification value is 194. 

0.40745 gms. of oil absorbed 0.6003 gms. of iodine from a 
solution of iodine and mercury bichloride in absolute alcohol. The 
iodine value hence is 147.4. 

To find out the neutralization value, 3.6638 gms. of the mixture 
were diluted with 50 c.c. of neutralized alcohol, a drop of phenol- 
phthalein solution added and titrated with a normal solution of 
caustic potash. It was found 12.64 c - c - were necessary for this 
purpose. Hence it follows that 193.2 mgms. of KOH were necessary 
for the neutralization of one gram of the mixture. The mean 
molecular weight is found by dividing 56.1 by that found necessary 
for the neutralization of one gm. of oil. 

Let M be the molecular weight and n the weight of KOH in gms. 

n 

now n = a X 0.0561 (a number of c.c.'s of riormal KOH). 

^1__ = jooo _ jooo > 8 

a X 0.0561 a 3.45 

3-33°3 gms. of oil gave 2.5847 gms. of liquid fatty acid by the 
lead-salt-ether process. Therefore, 77 per cent, of the total fatty 
acid was liquid fatty acid. 

It was found that the oil did not contain any stearic acid. 

The lactone value of the mixed fatty acid was the difference 
between the saponification and neutralization values, .8. 



54 Assay Process for Quinine in Tablets. { A ™eb/uary P i9iF' 

The titer test of temperature of turbidity of the mixed fatty acid 
is 22° C. 

The mixed fatty acid contains 8.14 per cent, of lauric acid as was 
found by fractional distillation of the oil in vacuo. 

Chemical Laboratory, Presedency College, Calcutta. 



AN ASSAY PROCESS FOR QUININE IN TABLETS. 
By Sidney F. Fieselmann, Peoria, 111. 

A rapid method for the quantitative estimation of quinine in 
tablets, containing no other chloroform soluble constituents, that are 
not expelled at a temperature of 125 C, which has been successfully 
used by the author with accurate results, is the following : 

Count out a sufficient number of tablets, so as to make the total 
number represent 10 grains of quinine or quinine salts, based on 
the quantity claimed on the label. If the quantity stated per tablet 
cannot be made to come out in a whole number of tablets, take the 
number of tablets, which contain about 10 grains and make the 
required correction. Weigh the tablets counted out accurately on an 
analytical balance. Multiply this weight by two and call it X grams. 
Then powder a sufficient amount of tablets and force all through a 
number sixty sieve. In case of coated tablets be careful not to 
loose any particle of the hard coating or parts of tablets during the 
process of powdering and sifting. Then mix thoroughly after this 
operation, so as to insure a uniform representative mixture. 
Weigh up X grams of this powder in a 100 c.c. Erlenmeyer 
flask, add 50 c.c. of chloroform, accurately measured, stopper 
and shake well. Now add 5 c.c. of ammonia water U. S. P., 
stopper well and shake thoroughly for 20 minutes. Let stand for 
about 12 hours in a cool place, with occasional shaking, and decant 
the chloroform into a separatory funnel, stopper well and allow to 
stand until separation takes place. Take a 5 cm. plain folded filter 
paper, on a small 60 glass funnel, moisten with a little chloroform, 
taking care not to have any chloroform drop into the measuring 
cylinder or any remaining in the tube of the funnel. Then withdraw 
enough of the chloroformic solution in the separating funnel and 
filter the same through the moistened filter paper into a 50 c.c. 
measuring cylinder until 25 c.c. are obtained. 



^'bra^iy P i9 a i4 m ' } Assay Process for Quinine in Tablets. 55 

If this 25 c.c. of filtrate is colorless or of a light straw color, 
transfer it to a tared beaker of 60-100 c.c. capacity, rinsing the 
cylinder with three portions of 10 c.c. of chloroform and adding the 
same to the chloroform solution in the tared beaker. Then evapo- 
rate the chloroform carefully on a water bath. If the filtrate is highly 
colored, from the coating, coloring matter, or resinous substances in 
the tablets, transfer the same into a clean separatory funnel, rinse 
out the cylinder as before, adding the same to the chloroform 
solution in the separatory funnel, and shake out with three portions 
of normal sulphuric acid, 15, 5, 5 c.c. respectively, each portion 
diluted with 5 c.c. of distilled water. Collect the combined acid 
aqueous solution in a clean separatory funnel, add a small piece of 
red litmus paper, make distinctly alkaline with ammonia water 
U. S. P. and shake out with three successive portions of 25, 15, and 
15 c.c. of chloroform, collecting the same in a tared beaker. After 
the chloroform has evaporated, redissolve the residue in 5 or 10 c.c. 
of ether and let evaporate spontaneously. 

Finally, place the tared beaker, containing the quinine residue in 
a drying oven and heat to a constant weight at 125 C, cooling the 
tared beaker each time in a desiccator before weighing. It usually 
requires from one to three hours of heating until the weight is con- 
stant. The tared beaker should be chemically clean and heated for 
at least one half hour at 125 C. and cooled in a calcium chloride 
desiccator, before it is weighed and the chloroformic solution added. 

If exactly 10 grains of quinine or the salts of quinine were taken 
as per label the residue should weigh the following : 



For Quinine Alkaloid U. S. P. (Quinine + 3H00) 0.5553 Grams. 

For Quinine Bisulphate U. S. P 0.3830 Grams. 

For Quinine Hydrobromide U. S. P 0.4963 Grams. 

For Quinine Hydrochloride U. S. P 0.5296 Grams. 

For Quinine Salicylate U. S. P 0.4457 Grams. 

For Quinine Sulphate U. S. P 0.4814 Grams. 



Tablets containing substances like calcined magnesia as a drying 
agent, do not filter rapidly by the above method. The water in the 
ammonia water forms a gelatinous mass with the magnesia, which 
prevents rapid filtration and sometimes stops it altogether. In that 
case the following method is suggested. Measure out in a 50 c.c. 
measuring cylinder, 5 c.c. of spirit of ammonia U. S. P., add a 
sufficient quantity of chloroform to make exactly 50 c.c. Use 



56 



U. S. P. ipoo Menstrua. 



{Am. Jour. Piiarm. 
February, 1914. 



this as a menstruum and follow the other directions as given 
above omitting the ammonia water. This last method cannot 
always be used on account of the alcohol in the spirit of ammonia 
U. S. P., which dissolves more substances than the chloroform would 
alone and so the residue would not be pure quinine. On the other 
hand chloroform alone will not dissolve anything but the quinine of 
the substances usually found in quinine tablets. 

In order to obtain sufficient chloroformic filtrate from tablets 
containing an unusual large quantity of other material and only 
a small amount of quinine, it may be necessary to increase the 
chloroformic menstruum from 50 c.c. to 100 c.c. or more, filtering 
off one half the quantity used, following the instructions given 
above. 

Sutliff and Case Co., Peoria, 111. 



U. S. P. 1900 MENSTRUA. 
By H. C. Hamilton. 

It seems almost superfluous to call attention, at this late date, to 
certain points in the 8th Revision of the U. S. P. which need correc- 
tion in the forthcoming 9th Revision. Particularly does it seem 
unnecessary in view of the fact that the objectionable features to 
which this article alludes have been pointed out before and by several 
critics. The excuse for doing so, however, if any is necessary, is 
that the data here published may be of value to those who have under 
consideration for the 9th Revision of the Pharmacopoeia the menstrua 
for the extraction of the digitalis series of heart tonics. The menstrua 
to which we refer are for the preparation of : I. F. E. Digitalis ; 
II. F. E. Squill ; III. F. E. Convallaria. 

I. The first two of these were referred to by Houghton and 
Hamilton 1 in the following words : 

" 3. Fluidextract digitalis, U. S. P. 8th Rev., 48 per cent, alcohol. 

" Average potency of eleven samples at time of manufacture 
55 H. T. U. per c.c. Three and a half years later 35 H. T. U. Aver- 
age loss about 10 per cent, yearly. 

" A very important point should be noted in this connection ; 
namely, the menstruum adopted in the last U. S. P. for the prepara- 
tion of fluidextract digitalis is much less desirable than the U. S. P. 
7th Revision in at least two respects. Repeated trials show that it is 



Am. Jour. Pharm. ) 
February, 1914. j" 



U. S. P. 1900 Menstrua. 



57 



almost impossible to get a finished product containing the full number 
of H. T. U. of the standard we had previously adopted, the average 
being as above stated, 55 H. T. U. per c.c, while with drug of the 
same quality when the 7th Revision menstruum is employed no diffi- 
culty is experienced. Owing to this it was decided to no longer 
attempt to assay physiologically the 8th Revision product and to 
take such statement referring to it off the label, but, in order to 
supply the medical profession with a full strength fluidextract of the 
drug, it was decided to prepare such with a menstruum containing 
a larger per cent, of alcohol which could be assayed and so labelled. 
In the second place the loss in potency of the 8th Revision is about 
10 per cent, per year, while with the 7th Revision it is less than 
one-half as great, or about 4 per cent. The results coincide quite 
closely with those following the change made in the menstruum for 
the fluidextract of squill except that the loss in activity was greater 
in the latter drug, as pointed out by Houghton 2 three years ago. In 
this paper several methods of physiological assay showed very 
clearly that a serious mistake had been made in changing to acetic 
acid as a menstruum. The writers feel certain that any one who has 
tried the 8th Revision menstruum for fluidextract digitalis has found 
that it is much less satisfactory from a pharmaceutical point of view, 
to say nothing of the loss in potency." 

To this we wish to add data since obtained on F. E. Digitalis as 
follows : 



The above samples were prepared from one lot of drug, using 100 
grams and extracting until exhausted. 

Another small sample of drug carefully extracted by both 
methods and tested gave results as follows : 



A sample of drug extracted with several strengths of alcohol gave 
the following results : 



Menstruum. 
50 per cent, alcohol . 
80 per cent, alcohol 



Per cent. Activity. 



IOO 



120 



with 50 per cent, alcohol 
with 80 per cent, alcohol 



no per cent, of standard. 
140 per cent, of standard. 



Menstruum. 



Per cent. Activity. 



94 per cent, alcohol 
75 per cent, alcohol., 
62.7 per cent, alcohol. 
50 per cent, alcohol. 



90 
140 
125 



no 



5« 



U. S. P. ipoo Menstrua. 



f Am. Jour. Pharm. 
\ February, 1914. 



The following table shows the tests of commercial lots of F. E. 
Digitalis, U. S. P. 8th Rev. (a) before and (b) after an attempt 
to improve the quality by concentrating the extract. 



Number. 


Tested. 


Per cent. Activity. 


I (a) 


8/4/9 


8=? 


i (b) 


8/19/9 


go 


2 (a) 


7/20/9 


85 


2 (b) 


8/4/9 


85 


3 (a) 


3/4/9 


60 


3 W 


4/2/9 


100 


4 (a) 


I/3I/8 


80 


4 (b) 


2/8/8 


80 


5 W 


5/23/7 


75 


5 (b) 


6/1/7 


83 



Further data on 20 samples of the preparation show results of 
first tests ranging from 50 to 100 per cent, standard and averaging 
exactly 78 per cent. 

The standard referred to is the average activity obtained from 
12 lots of crude drug, botanically of first class quality, selected at 
random and extracted with 62.7 per cent, alcohol, the official men- 
struum of the U. S. P. 7th Revision. The activity was determined 
by the frog method described by Houghton 3 as a means of standard- 
izing the heart tonics of the digitalis series. In that article attention 
was called to the enormous variation in samples of the crude drug for 
sale on the open market. 

The value of such a method is also shown when endeavoring 
to extract from active material all the therapeutically active sub- 
stances and to establish by experiments on other than the human 
subject the relative activity of extracts obtained by means of various 
menstrua. 

The above results speak for themselves, but if additional authority 
is needed it should be sufficient to note that the menstrua for making 
tinctures and fluidextracts of digitalis in the official Pharmacopceise 
of the world, specify, almost without exception, a percentage of 
alcohol in excess of that official in the U. S. P. 8th Revision. The 
menstruum adopted in 1906 by the Brussels Conference is 70 per cent, 
alcohol and it is to be hoped that the Revision Committee will be 
influenced by this in adopting an official menstruum for the 9th 
Rev. of the U. S. P. 

II. As noted before in the abstract from: the American Journal 



Am. Jour. Pharm. \ 
February, 1914. / 



U. S. P. 1900 Menstrua. 



59 



of Pharmacy 1 a mistake was certainly made in adopting for the 
preparation of F. E. Squill, U. S. P., 8th Rev., a menstruum com- 
posed of a 10 per cent, solution of Acetic Acid. This is so far from 
being ideal for extracting the active substances from Squill bulb that 
it is practically impossible to prepare an extract representing the 
activity of the crude drug. 

Comparison of the activity of F. E. Squill, U. S. P., 1890 and 1900, 
was made by Houghton 4 as follows : 

" Comparative Strength of Fluid Extract of Squill Prepared from 
the Same Lot of Drug According to the United States Pharmacopoeia 
of 1890 and 1900: 

" 1 U.S. P., 1890, 140 per cent, as active as standard fluid extract. 

" 2 U.S. P., 1890, 140 per cent, as active as standard fluid extract. 

"3 U.S. P., 1900, 60 per cent, as active as standard fluid extract. 

"4 U.S. P., 1900, 60 per cent, as active as standard fluid extract. 

" It may be observed that activity of both products is high as com- 
pared with the results given in Table 2. This probably is due to 
the great care exercised completely to exhaust the drug and to the 
high quality of the drug. 

" In order to meet any objections that might be offered against 
the results as shown by the special method of assay employed, the 
work was checked by experiments on dogs showing the comparative 
activity of the two products in producing changes in the blood-pres- 
sure, which is perhaps the most characteristic physiologic action of 
the members of the digitalis series/' 

The results of the latter experiments are here recorded in tabular 
form for more convenient reference. 

Experiment I. 

F. E. Squill, U. S. P., 1890. F. E. Squill, U. S. P., 1900. 
Before After 
injection. injection. Before. After. 

Pulse Rate 100 96 116 138 

Blood-pressure 46 54 48 45 

In this experiment 0.3 c.c. F. E. Squill, U. S. P., 1890, was injected 
at 10.45 A - M - in* the femoral vein of an anaesthetized dog. Then 
at 2.41 p.m., when the effect of the first injection had passed, the 
same amount of F. E. Squill, U. S. P., 1900, was injected. 

In the second experiment the order of injection was reversed an- 
other dog being used for the test, and the same amount of each 
preparation injected. 



6o 



U. S. P. 1900 Menstrua. 



f Am. Jour. Pharm. 
( February, 1914. 



Experiment II. 



Pulse Rate . . . 
Blood-pressure 



F. E. Squill, U. S. P. , 1900. 

Before. After. 
. . . 102 I44 



F. E. Squill, U. S. P. ,1890. 



Before. After. 
IOO 94 
52 50 



47 46 



Note. — In both cases the U. S. P., 1900, preparation increased the 
rate and lowered the pressure. This is directly opposite in effect 
from the characteristic action of the heart tonics in general and from 
that of the F. E. Squill, U. S. P., 1890, from the same drug. 

In this case again a stronger alcohol is better. If the drug is 
finely ground and extracted with menstrua containing 60 per cent, 
or less of alcohol, it swells so that percolation is either entirely or 
almost prevented. It becomes necessary either to cut the bulb without 
grinding or toi mix with sawdust in order to have it sufficiently open 
to percolate properly. An additional objection is in the large amount 
of gummy, water-soluble extractive obtained with such menstrua. 
A fluid extract of better appearance, better keeping quality and con- 
taining practically all the available activity of the drug, can be 
obtained by the use of 80 per cent, alcohol. Repeated experiments 
have shown the excellence of this menstruum over that of the 7th or 
8th Revisions of the U. S. P. 

III. Fluid Extract Convallaria, U. S. P., 1900, is not so open 
to criticism as the others but the menstruum is not entirely satis- 
factory. There are certain advantages to be gained by using a 
stronger alcoholic menstruum than that prescribed in the 8th Revis- 
ion U. S. P. While these advantages are more apparent when 
experiments are conducted on a manufacturing scale than when 
small experimental lots of fluid extract are prepared, even in the 
latter case the advantages are very real. 

Several experiments have been carried out, of which the following 
is used as an example : 

A small lot of drug was divided into two portions, one of which 
was extracted as prescribed in the U. S. P. ; namely, with 62.7 per 
cent, alcohol, the other with 80 per cent, alcohol. These extracts were 
carefully concentrated to fluid extract volume and tested for activity 
by the method previously cited, with the following results : 



Menstruum. 

62 per cent, alcohol 
80 per cent, alcohol 



Per cent. Activity. 
IOO 
I20 



Vebi J uTiT, P i h 9T4 m ' } Standardisation of Heart Tonics. 61 

The advantages to be gained from using a stronger alcoholic men- 
struum for extracting cdnvallaria roots and rhizome are not merely 
the greater activity obtainable, but in the improved appearance of 
the extract and its greater stability. It contains less of the gummy 
extractives and more alcohol, both of which are desirable features, as 
they affect deterioration, while the 20 per cent, increase in activity 
from the use of 80 per cent, alcohol is no less desirable. 

It is to be hoped that those in charge of revising the forthcoming 
U. S. Pharmacopoeia will consider these suggestions. 

LITERATURE CITED. 

1 American Journal of Pharmacy, October, 1909. 

2 Jour. American Medical Ass'n., June 12, 1906. 

3 Ibid., September 11, 1897. 

4 Ibid. , May 12, 1906. 

From the Research Laboratory of Parke, Davis & Co., 

Detroit, Michigan. 



THE PHYSIOLOGICAL STANDARDIZATION OF THE 
HEART TONICS.* 

By Professor William A. Pearson, of The Hahnemann Medical College 

of Philadelphia. 

" The Physiological Testing of the Heart Tonics," which is the 
subject assigned for my discussion, is a very inaccurate title. 

A satisfactory definition of a tonic has never been given, much 
less, a heart tonic. The word physiological is not appropriate be- 
cause when any active drug is given the normal processes of the body 
are no longer physiological. 

For these reasons, such a subject as " The Pharmacologic Stand- 
ardization of Drugs Having a Particular Action on the Heart " would 
be far more fitting. 

Since Digitalis is the most important member of the group of 
drugs known as " heart tonics," a discussion of the methods of 
standardizing this drug will be first considered. 

Medicinal Use and Therapeutic Action of Digitalis, 
It is well known that Digitalis has had a place in domestic and 
medicinal therapy for centuries, and many of you know that a Bir- 



* A special lecture given at The Philadelphia College of Pharmacy, De- 
cember 8, 1913. 



62 Standardisation of Heart Tonics. {^ebruar'y,^™' 

mingham physician by the name of Withering, 1 published in 1785 the 
first reliable observations of the medicinal properties of this drug. 
The diuretic properties of Digitalis were first observed, but after 
the middle of the last century its ability to< slow the heart so impressed 
the medical profession that Digitalis was, and is even to this day, 
often used indiscriminately for all conditions where the heart beat 
is irregular or rapid. It can now be demonstrated that Digitalis is 
only of particular value in a very limited number of diseases of the 
heart and mainly in auricular fibrillation. 

So far as showing the rate of the heart beats is concerned, it may 
be laid down as a law, that Digitalis is far less effective when the 
rhythm of the heart is normal than when there is auricular fibrillation. 2 
Most authors state that digitalis causes constriction of the blood- 
vessels and consequently a rise in blood-pressure, yet I have not been 
able to demonstrate more than slight variations in blood-pressure in 
test animals, although various lots of tinctures, fluid extracts and 
proprietary preparations have been tried. 

Mackenzie 3 has made numerous observations on various classes 
of patients and refutes the idea that the administration of Digitalis 
has a tendency to produce fatal syncope, provided the drug is stopped 
as soon as nausea and vomiting appear or when the heart rate falls 
below 50 per minute. 

When the rhythm of the heart is normal the first symptom is loss 
of appetite, if drug is continued, vomiting, feeling of malaise, head- 
ache, and very little diarrhoea may be reported. 

Famulener and Lyons 5 state that the digitalis glucosides act not 
only on the heart but directly on the central nervous system, first 
stimulating then depressing it. Cushny 6 states that " the chief thera- 
peutic use is to counteract certain changes in the circulation, which 
result in the blood accumulating in the veins in too large quantities 
while the arteries are less filled than usual. In cases of dilation of 
the heart with a weak and insufficient systole, its action is almost 
specific. 

" In these cases the action is very simple — the increased ventricu- 
lar systole approaches the normal, the output of the heart is increased, 
and in some cases the dilation is diminished by the direct action of 
the drug. The effect is an increased velocity and pressure in the 
arteries and improved nutrition of the whole body." 

There is no doubt that Digitalis relieves distress and dropsy and 
has been directly responsible for numerous cures, yet it is possible 



A Febraai r y ^iuET' } Standardization of Heart Tonics. 63 

that these favorable results may be attributed to some other reason 
than its effect on the heart, per se. 

It is needless to say that Digitalis has been given thousands of 
times when its use was not indicated and doubtless its failure to pro- 
duce favorable results under improper conditions has been responsible, 
more than once, for condemnation of the particular preparation of 
digitalis being used. 4 It has been repeatedly stated that analogous 
preparations of digitalis made by various manufacturers differ mark- 
edly in strength, that digitalis preparations rapidly deteriorate and 
that only the leaves of the first year's plant are active. It is no doubt 
true that analogous digitalis preparations differ markedly in strength, 7 
but it is very doubtful if the usual galenical preparations deteriorate 
rapidly, 8 or that only the leaves of the first year's plant are active. 9 

It is possible, but not at all probable, that only the digitalis plants 
which are in flower are physiologically active and this need not ex- 
clude the first year's plants as John A. Bornemann 10 has shown me 
a digitalis plant with plenty of flowers on it, although it was a plant 
of the first year's growth. Certain it is that the therapeutic action 
of digitalis as stated by various authors is sadly confusing and no 
doubt much of this confusion is due not alone to clinical reports where 
digitalis was not indicated, but to the pharmacologic variability of the 
preparations themselves. 

Chemistry of Digitalis. 

Almost every pharmaceutical chemist of note has tried to isolate, 
unchanged, the complex active principles that are present in digitalis. 
The great Schmiedeberg and Kiliani agreed that the four glucosides 
which they separated and called digitoxin, digitalin, digitalein and 
digitophyllin, possess a true digitalis action. They separated, in addi- 
tion, other glucosides such as digitonin, digitin and digitoflavin, but 
they considered these decomposition products. Several carbohy- 
drates which came from the decomposition of the glucosides, were 
also described. 

When one looks up the vast literature on the chemistry of digitalis 
it is quite evident that different glucosides are sometimes given the 
same name by different authors and vice versa. 

Recently Kraft 11 has contributed an admirable article on this 
subject and his work is now generally accepted. He claims that both 
Schmiedeberg and Kiliani worked with German digatalin, a commer- 
cial product made largely from digitalis seeds, hence their results are 



64 Standardisation of Heart Tonics. { A ^ u °^^ a - 

not reliable for digitalis leaves. Kraft has isolated a new active 
glucoside which he calls Gitalin, which probably has the chemical 
formula C 28 H 48 O 10 . This glucoside is amorphous but forms a 
crystalline hydrate, C 28 H 48 O 10 4H 2 O. Gitalin readily decomposes in 
any solvent except chloroform into anhydrogitalin C 23 H 46 9 which on 
hydrolysis, with a dilute acid in the presence of alcohol, changes to 
anhydrogitaligenin C 22 H 34 5 and a sugar which was found to be 
identical with Kiliani's digitoxose. Another new glucoside was also 
isolated. This he called Gitin, and it is inactive physiologically. It 
is crystalline and melts at 265 ° C. It is considered similar to, but not 
identical with, Kiliani's digitonin. 

Digitoxin is often considered the chief active glucoside in digitalis 
and chemical determinations of this constituent have been frequently 
made in the hope of finding a relationship between the digitoxin con- 
tent and the therapeutic activity, but the results in almost every case 
have proved a failure. 12 If the digitoxin from a given amount of 
drug is isolated it will be found that the total amount of digitoxin is 
very much less toxic than the amount of drug from which it was 
obtained, hence it seems absolutely necessary to resort to pharmaco- 
logical standardization if any definite idea of the therapeutic strength 
is desired. 

Pharmacologic Standardization of Digitalis. 
At least three distinctly different pharmacologic methods have 
been proposed for the standardization of Digitalis — the frog method, 
the guinea pig method, and the cat method. 



The Frog Method. 
The frog method was first proposed by Houghton in 1898. 13 He 
found that " fairly accurate data could be obtained from the appli- 
cation of a solution containing Strophanthin, Digitalin, etc., to the 
laid-bare frog's heart, by comparing the action of the drug thus 
tested with that of a sample of known strength." After much ex- 
perimental work this method was replaced by the use of a simpler 
one — namely, the determination of the minimum lethal dose for frogs 
under definite conditions. Although the original method as modified 
by Houghton gives quite satisfactory results, yet various workers 
have proposed certain changes in the conditions under which the test 
is to be made. For example, twelve hours was specified as being the 
length of time that observations should be made after injection of the 



A Fe'braa^y *m£' } Standardisation of Heart Tonics. 65 

frogs. As this is usually inconvenient, these observations were 
made after one hour, two hours, six hours, or twenty-four hours. 
Some workers began to pith the frog at the end of one hour and 
make a direct examination of the condition of the heart, for it was 
found that sometimes frogs would be apparently normal yet their 
hearts had been stopped by the drug. 

Dr. Hale 14 observed that more concordant results were obtained 
when the frogs were kept at the uniform temperature of 22 C. It 
would neither be interesting nor instructive to relate the various modi- 
fications that have been proposed for the Houghton method. 

Edmunds and Hale, 15 Edmunds and Cushny, 16 and Focke 17 have 
specified various conditions under which the " frog test " is to be 
made, but none of these methods make any provision to 1 standardise 
the frogs that are used. 

It is known that variety, weight, sex, season, and temperature 
affect the resistance of frogs and hence it is possible to> obtain different 
results with different lots of frogs. In order to eliminate these factors 
of unknown significance in any particular case, Houghton and 
Hamilton have suggested that a standard be used in testing the 
resistance of every lot of frogs, at the time the test is made. Upon 
these data " The Heart Tonic Unit " 18 is computed in every case. 

The standard they propose to use is crystalline Strophanthin 
which is prepared from an authentic specimen of the official drug, 
Strophanthus Komibe, and has been studied in detail by Braun and 
Closson. 19 The outline of the present method as modified by Hough- 
ton is as follows : 

Frogs should all be of same species, a convenient variety is the 
Rana Pipiens. They should all be of weights between 15 and 35 gm. 
and the weights should not vary more than 25 per cent, in any one 
assay. Before being used the frogs may be kept in any convenient 
place where the water can be frequently changed and kept at a tem- 
perature of about 22 C. During the test the frogs can advan- 
tageously be kept in wire cages with sheet iron bottoms, standing 
in trays of running water, but the depth of water in the cages should 
not exceed one-half an inch. Scales for weighing the frogs should be 
accurate within 0.5 gm. The necessary apparatus consists of volu- 
metric flasks, cylinders, graduated pipettes and a 1 c.c. pipette 
graduated in hundredths of a cubic centimetre and fitted with a hypo- 
dermic needle or drawn out into a fine point for injecting. 



66 Standardisation of Heart Tonics. { February P i9i™' 

The solution to be injected should not contain more than 10 per 
cent, alcohol and the dilution should be made with physiological salt 
solution (0.85 per cent. NaCl). 

The doses are calculated on the weight of the frog, i.e., the 
M. L. D. is the minimum lethal dose, per gram weight of frog. 
For example, when the frogs are of average resistance the M. L. D. 
of Strophanthin is 0.000,001 gm. per gram weight of frog, i.e., for a 
30 gram frog the lethal dose of Strophanthin is .000,03 g m -> which 
should be so diluted that this amount is contained in approximately 
0.5 c.c. Several series of tests are necessary to establish the activity 
of any sample of unknown strength and since the frogs vary in 
resistance among themselves and also because of conditions more or 
less beyond control, the standard Strophanthin must be tested at the 
same time. When the M. L. D. of sample and of standard are 
obtained the activity can readily be expressed in Heart Tonic Units 
(H. T. U.) by reference to a table. 

In the method just given the observations are to be made at the 
end of twenty-four hours, hence the one-hour method has certain 
advantages when several series are desired on a single sample as soon 
as possible. When the one-hour method is used it is necessary to not 
consider all frogs that have not absorbed the dose injected. 

The One-Hour Method. 

" In this method the frogs are secured and kept in the manner 
already described, weighed, and such a dose is injected that the 
heart will be found in complete systolic contraction at the end of 
exactly sixty minutes. The drug, properly diluted so as to make 
a volume of 0.5 to 1 c.c, is injected into the anterior lymph sac by 
means of a glass pipette. Shortly before the hour is up the frog is 
pithed, tied to a frog board, and the heart is exposed in the usual 
manner. If the heart is still beating, the dose has been too small 
and must be increased in subsequent trials. In the first series doses 
are chosen with wide limits, which in a second and third series of 
animals are narrowed down until the smallest amount of the drug 
which will produce systolic standstill in one hour is found. Usually 
three series of frogs are sufficient to assay one preparation, but in 
case of any irregularity in the reaction of any of the frogs a fourth 
or even a fifth series may be necessary." 

The method of Focke 17 is long and complicated and does not 
appear to have any advantage over the other frog methods that have 
been described. 



Am. Jour. Pharm. ) 
February, 1914. j 



Standardisation of Heart Tonics. 



6 7 



Guinea Pig Method. 

Reed and Vanderkleed 20 first advocated the advantages of using 
the guinea pig as the test animal although Houghton 13 had pre- 
viously tried pigs but considered the frog test more reliable. 

The closer biologic relation of the guinea pig to man appears to 
be one important reason for preferring guinea pigs. It is claimed 21 
that " frogs not only show the pharmacological action of the drug 
under test, but they react with so near an approach to uniformity that 
the medicinal value of a tested specimen can be gauged by the deter- 
mination of the minimum fatal dose — for the slowing of the heart 
beat and the systolic emphasis produced by active heart tonics are 
directly proportioned to the quantity of the drug administered, and 
under progressive doses at last reach a point which is incompatible 
with life." 

Details of Reed and Vanderkleed Method for Testing Digitalis 
and its Preparations. 

If Digitalis leaves are to be tested a tincture is first prepared 
from the sample by the U. S. P. process. 

An amount of any alcoholic preparation representing one-tenth 
of a gramme of Digitalis Leaves is placed in a very small watch glass 
and the excess of alcohol evaporated from it at room temperature 
by placing the vessel in a current of air. This residue is then care- 
fully washed into a Hitchen's syringe 22 with sufficient physiologi- 
cal salt solution to make the total volume two cubic centimetres. 

The hypodermatic needle is previously sealed with sufficient petro- 
latum to prevent loss of this solution. 

Two cubic centimetres of physiological salt solution is placed in 
the side-arm of the syringe and the needle inserted under the skin 
of a guinea pig weighing about 250 gm. 

The solution of the drug is then injected and the last portions 
washed under the skin with the physiological salt solution which was 
placed in the side arm, without removing the needle. 

Great precaution is taken to inject accurate amounts and always 
a total of four cubic centimetres of liquid (2 c.c. of solution of drug 
and 2 c.c. of physiological salt). 

After the injection, the guinea pig is kept under close obser- 
vation and evidences and time of salivation, purgation and convul- 
sions noted. If the pig should not develop these symptoms and die 
within two hours, another pig is injected with a larger quantity of 
the drug. 



68 Standardisation of Heart Tonics. {^Zy^oit 

The tests are repeated until the amount of the drug is found 
which will produce the characteristic symptoms of Digitalis poisoning 
and kill a 250 gm. guinea pig in two hours. 

Post-mortem examinations are always made to note the con- 
dition of the heart and dilation of the blood-vessels. 

In testing solid preparations of Digitalis a weighed quantity of 
the preparation is shaken with a definite amount of physiological 
salt solution so that two> cubic centimetres of the liquid will represent 
one-tenth gramme of the drug. This method has been found quite 
satisfactory, but Pittinger 23 has found that more concordant results 
are obtained if the time of observation is extended from two hours 
to twenty-four hours. One disadvantage to the method is that the 
cost of the required pigs is usually greater than the frogs necessary 
for Houghton's method. This objection is largely overcome by manu- 
facturers of antitoxin who can use the pigs that have survived the 
antitoxin tests for digitalis tests. These pigs cannot again be used 
for testing serum on account of anaphylaxis, and by the time they 
have completely recovered from the antitoxin tests they may weigh 
much more than 250 gm., which is the weight specified. No pro- 
vision is made for the varying susceptibility of the pigs and it is 
doubtful if the pig test, as it is usually carried out, will give any more 
reliable results than a larger number of frogs that have been " stand- 
ardized " with crystalline strophanthin. 

The Cat Method of Hatcher and Brodie. 24 

This method is based upon the determination of the minimum 
lethal dose for cats. The cat is anaesthetized with ether and about 
one-half of the amount of the preparation being tested necessary to 
kill the animal is injected directly into the venous circulation. The 
originators of this test have found that if preparations of digitalis or 
other members of this series are injected until the cat dies, the results 
will usually be too high, hence, after twenty minutes a 1 to 100,000 
solution of Merck's Ouabain is cautiously injected until the cat shows 
signs of dying, namely, rapid respiration, which soon becomes irregu- 
lar and is accompanied by convulsive movements. The Ouabain 
should be injected in such amounts that the cat should die ninety 
minutes after the beginning of the test. 

The " cat unit " is the amount of crystalline Merck's Ouabain 
which is fatal within about ninety minutes to each kilogram body 



Ve'braary, P i h 9 a i r 4 m '} Standardization of Heart Tonics. 69 

weight of the cat. This amounts to 0.1 milligramme of the Ouabain 
and the number of " cat units " in one cubic centimetre of the prep- 
aration being tested is computed from the data obtained. Eckler 25 
has reported serious disadvantages to this method, and it is doubtful 
if it will ever have the popular favor the other two methods enjoy. 

Factors Relating to the Standardization of Digitalis. 

It may easily be seen that the last word has not been said in 
regard to the standardization of Digitalis and this unsettled condition, 
in its standardization, is certain to prevail until the therapeutic uses 
and chemistry of the drug are agreed upon. 

It is true that some fault can be found with the methods we have 
outlined and no doubt many factors will soon be eliminated. 

At the present time, it is possible to determine by physiological 
tests with reasonable accuracy the variability of the crude drug, the 
stability of its preparations, and to prepare preparations of con- 
siderable uniformity. 26 

Other Heart Tonics. 

What has been said in regard to the methods used for standard- 
izing Digitalis applies also to preparations of Strophanthus, Squill and 
Convallaria. Strophanthus seems to be more certain in its action 
than digitalis and can also be advantageously tested by the blood- 
pressure method upon dogs. 

Cactus grandiHorus has long been used empirically with appa- 
rently favorable results, yet competent pharmacologists have reported 
that it has no action analogous to digitalis 27 ' 28 . Graeber 29 has 
recently reported the presence of both alkaloids and glucosides in 
this drug and publishes experiments on frogs which " indicate that 
Cactus grandiflorus actually is possessed of an action upon the heart 
such as belongs to the substances of the digitalis group." In all his 
frog experiments the frequency of the pulse was reduced and the 
systole strengthened. 

Sparteine sulphate is considered a drug of mediocre importance 
as a " heart tonic," yet Pettey 30 considers that Sparteine is unappre- 
ciated because it is not given in sufficient doses. He recommends the 
use of 2 grain doses as a true and reliable heart tonic, an excellent 
non-irritating diuretic and states that this dose is entirely free from 
untoward or objectionable effects. 



70 Standardisation of Heart Tonics. { A ?eb™?S, P i»i™' 

Work of the Normal Heart. 
Few realize the vast amount of work performed each day by the 
heart of the normal adult. One-fifth the total muscular energy of the 
body is used in propelling the heart and about twelve tons of blood 
are pumped each day. 

New Methods of Observing Conditions of the Heart. 
The electro-cardiographic method 31 has made possible not only 
the accurate diagnosis of diseases of the heart but also enables the 
physician to observe the effects of the medicine he has prescribed. 
The practice of medicine under these conditions has become scientific, 
not empiric, and if uniform preparations of the " heart tonics " can 
be supplied, the physician needs only to consider the idiosyncrasy of 
the patient. 

Summary. 

In presenting this subject I have attempted to dwell not alone on 
the methods used in standardizing the " heart tonics " but the various 
factors that must be considered in producing reliable and potent prep- 
arations. The clinical side of the problem must not be lost sight of, 
and when a preparation is made that will produce certain therapeutic 
results it is of vital importance to produce another lot having the 
same action. Uniformity is practically as important as potency. 
When a competent observer like Faught 32 says " Usual preparations 
are variable and cannot be depended upon unless coming from a 
reliable source. I have seen less effect follow the administration 
of 20 minims of a poor preparation than 5 minims of a good active 
one " it is time to improve conditions. Conditions can be improved 
by the adoption of pharmacological standards and methods for these 
drugs. At the present time the manufacturers who have wisely 
adopted physiological standardization of their products often have 
different standards while those that have not adopted physiological 
standards have no assurity that these important drugs are even active. 

- BIBLIOGRAPHY. 

1 Withering, " An Account of the Foxglove and Some of its Medicinal Uses." 

2 Mackenzie, " Digitalis " Heart, volume 2, No. 4, page 279. 

3 Mackenzie, " A Scheme for Investigating the Treatment on the Human 

Heart " Heart, volume 2, page 9. 
* Berkeley, Merck's Archives, September, 1910, page 275. 

5 Proceedings of American Pharmaceutical Association, 1902, page 415. 

6 Cushny, " Pharmacology and Therapeutics." 



Am. Jour. Pharm. ) 
February, 1914. j 



Colloids and Crystals. 



71 



T Journal of Amer. Med. Assoc., September 13, 1913. 

8 " Observations on the Keeping Properties of Digitalis and Some of Its Prep- 
arations," Hatcher and Eggleston. American Journal of Pharmacy, 
1913, page 203. 

9 Miller and Baker, 8th International Congress of Applied Chemistry. 

10 Personal Communication. 

11 Kraft, Arch, der Pharm., 1912. 

V£ Edmunds and Hale, " The Physiological Standardization of Digitalis." 
18 Houghton, Journal of American Medical Association, June 7-10, 1898. 
"Hale, The Physiological Standardization of Drugs, American Journal of 
Pharmacy, 191 1. 

16 United States Hygienic Laboratory, Bulletin 48. 

18 " Laboratory Guide in Experimental Pharmacology," Geo. Wahr, publisher. 

17 Focke, Arch. d. Pharm., 1903, 241, page 678. 

18 Hamilton, " The Heart Tonic Unit," American Journal of Pharmacy, 1912, 

page 97. 

19 Braun and Closson, " The Chemical Constitution of Crystalline Strophan- 

thus," Jour, of Amer. Pharm. Assoc., 1913. 

20 Reed and Vanderkled, American Journal of Pharmacy, 1908, page no. 

21 " Standardization of Pharmaceutical and Biological Products," Parke, Davis 

and Co. 

22 Hitchens. Journal of Experimental Medicine, 1905. 

23 Pittinger, 1912 Proceedings American Therapeutic Society. 

34 Hatcher and Brodie, American Journal of Pharmacy, 1910, page 362. 

25 Eckler, American Journal of Pharmacy, October, 191 1. 

26 Hale, Factors Relating to the Standardization of Digitalis ; Proceedings of 

American Pharmaceutical Association, 1909. 

27 Hatcher and Bailey, Jour. Amer. Med. Assoc., 1907, page 1021. 

28 Lyon and Quail, Jour. Amer. Med. Assoc., 1910, pages 455, 459, 508. 
19 Graeber, Therapeutische Monatshefte, 1913, page 581. 

30 Pettey, " The Therapeutic Virtues of Sparetine Sulphate." Clinical Medi- 

cine, Sept., 1913. 

31 Lewis, " Clinical Electrocardiography." 

52 Faught, " Blood-Pressure from Clinical Standpoint," page 268. 

COLLOIDS AND CRYSTALS, THE TWO WORLDS OF 

MATTER* 

By Robert H. Bradbury, 
Head of the Department of Science in the Southern High School, Philadelphia. 

When a solid is brought into contact with a liquid the result 
depends upon the nature of both. There may be apparently an entire 

* Presented at the meeting of the Section of Physics and Chemistry held 
Thursday, April 10, 1913, and reprinted from Jour. Franklin Institute, Sep- 
tember, 191 3. 



72 



Colloids and Crystals. 



j Am. Jour. Pharm. 
( February, 1914. 



absence of interaction, as when rosin is shaken up with water or chalk 
with alcohol. Or, as when sugar is agitated with water, the solid 
may disappear, entering into solution in the liquid. The study of 
sugar solution shows quite clearly that the connection of the sugar 
molecules with each other has been completely destroyed. They are 
dispersed through the water very much as the molecules of a gas 
distribute themselves uniformly in a vacant space, and in both cases 
the permanence of the uniform dispersion is due to the incessant 
motion of the molecules. Were the molecules at rest, both the sugar 
and the gas would settle and form a layer on the bottom of the 
containing vessel. 

However, the molecules of the sugar retain their structure intact, 
the action being limited to their dispersion. When salt, on the other 
hand, is dissolved in water, a further breakdown occurs, the molecule 
is separated and ions of sodium and of chlorine move about in the 
liquid. Both solutions freeze below o° C. and boil above ioo° C. 
The most important difference between them is that the salt solution 
conducts the electric current, while the sugar solution is as poor 
a conductor as water itself. 

A fourth possibility presents itself when glue or gelatin is treated 
with water. The gelatin absorbs water, swells up and, under the 
influence of heat, dissolves, but the liquid freezes and boils at prac- 
tically the same temperatures as pure water. The study of the solu- 
tion shows that the dispersion is not molecular. The particles of 
gelatin in it are composed of variable and rather large numbers of 
molecules. A system like this gelatin solution which presents a case 
of very fine but not molecular subdivision is called a colloidal solution. 
There are certain solids such as gelatin and dextrin (with water), 
and rubber (with benzene and carbon disulphide), which, when they 
dissolve in liquids, are invariably dispersed in this way. Such solids 
may properly be referred to as colloids. They are all amorphous. 
Crystallized substances never yield colloidal solutions by mere spon- 
taneous solution in a liquid. They always produce molecular or 
ionic dispersions. However, the phenomenon of colloidal solution is 
perfectly general, and crystallized substances can also be obtained 
in this condition, but not by mere solution. 

It is an interesting fact that a substance which yields a colloidal 
solution with one solvent may form an ordinary molecular solution 
with another. Soap is an example. Its concentrated solution in 



Am. Jour. Pharm. ) 
February, 1914. J 



Colloids and Crystals. 



73 



water boils at about ioo°, freezes at about o°, and exhibits the be- 
havior of a colloidal solution in general. On the contrary, a soap 
solution in alcohol shows the normal change in freezing and boiling 
points corresponding to the molecular weight, and conducts itself in 
all respects like an ordinary molecular dispersion. 

II. 

Every one is familiar with the distinctions between solutions and 
suspensions. Suspensions are turbid in aspect, and the solid can be 
removed by letting it settle, or by nitration. Solutions are clear, dis- 
solved matter does not subside and is unaffected by filtering. Col- 
loidal solutions occupy an intermediate position. 

Consider for a moment the effect of increasing subdivision on 
a suspension of finely-divided gold in water. So long as the diameter 
of the particles is much greater than a thousandth of a millimetre, 1 
the system will be turbid and the gold will settle rapidly. But the 
wave-length of visible light ranges between 0.4 \x and 0.7 /x, and 
when the particles become smaller than this they can no longer reflect 
light and the liquid will appear clear. At the same time there will 
be a rapid falling off in the speed of settling. Stokes has derived a 
formula for the velocity of subsidence, V , of small spheres of radius 
R and density ^ falling in a liquid of density S' and internal friction / 
under the force of gravity g: 

Substituting the proper values for gold and water and assuming 
a radius of /x for the particles, the value for V is about 14 centi- 
metres per hour. This means, of course, that the system would be 
a coarse suspension and would clear up at once. But when 
R = 10 fx fx, V is only about a centimetre a month. This begins 
already to be fairly permanent. It must be remembered that the 
high density of gold (19.5) increases the rapidity of subsidence. 
If we make the calculation for S = 3, which is about the density 
of arsenious sulphide, V comes out only about a millimetre a month. 



1 It is usual to employ the symbol v> (the Greek letter mu) for the thou- 
sandth of a millimetre. In the same way ix fx indicates the millionth of a 
millimetre. 



74 



Colloids and Crystals. 



Am. Jour. Pharm. 
February, 1914. 



So much for calculation. Now what are the facts ? As a matter 
of fact, the dispersed substance in a colloidal solution does not settle 
at all, so long as the subdivision is maintained. Colloidal gold solu- 
tions have been preserved unchanged for years. I have a solution 
of arsenious sulphide which has remained apparently unchanged for 
three years and whose countless particles can readily be seen, engaged 
in their incessant Brownian movement, with an ordinary oil immer- 
sion lens. Whenever settling does occur, it is preceded by the 
aggregation of the particles into' larger particles, which finally attain 
a diameter of fx or over, and slowly subside. 

Here, then, is an apparent discrepancy between Stokes' law and 
the facts. The law informs us that the speed of subsidence decreases 
rapidly with decreasing radius of the particles, but it does not lead 
us to expect the total absence of settling which presents itself when 
the average radius is 10 f- /* or thereabout. 

The explanation, of course, is molecular motion, or, in other 
words, heat. The particles are battered, on all sides, by a hail-storm 
of molecular impacts. If the particle is large, the blows of the mole- 
cules of the solvent in different directions neutralize each other. 
But when the particle is not so very much larger than the molecules 
themselves a molecule striking, say on the left, will give the particle 
a very perceptible push toward the right, "just as a cork follows better 
than a large ship the motion of the waves of the sea." 2 As the 
dimensions of the particle approach the molecular dimensions it 
begins to behave like a molecule and is swept along in the endless 
molecular movement. The cause which prevents the particles in a 
colloidal solution from settling is in no way different from the cause 
which prevents the earth's atmosphere from subsiding to a snowy 
layer a few feet deep on the surface of the planet. 

It is worth remembering, also, that the particles of the dispersed 
phase ordinarily possess an electric charge, which is usually negative. 
The effect of the repulsion of these similar charges would be to* pre- 
serve the distribution of the particles throughout the liquid. It is a 
fact that, when the charges are removed, the system becomes instable 
and subsidence — preceded by coalescence of the small particles — 
readily, but not necessarily, occurs. 



2 Perrin. 



Am. Jour. Pharm. ) 
February, 1914. j 



Colloids and Crystals. 



75 



III. 

On the subject of the classification of colloid systems we must 
be very brief. One proposal subdivides them into suspensoids, such as 
the sols 3 of gold and arsenious sulphide, in which the dispersed 
phase is solid, and emulsoids, in which the dispersed phase is liquid. 
This classification would appear to be an attempt to extend the 
familiar distinction between liquid and solid to a domain in which 
that distinction has little if any meaning. To assert that a thing is 
solid is to say that it has a definite shape, which it retains with some 
persistence. There is not the slightest reason to think that the 
particles in a gold sol are solid. It is usual to assume that they are 
spherical, but this is done merely because it is the simplest assumption 
to make. There are faint indications that they really have the form 
of leaflets or of little rods, but they appear in the ultra-microscope 
simply as brilliant dancing points, and in reality we know nothing 
whatever about their shape. In connection with this it is interesting 
to recall the fact that the formation of a crystal begins with the 
appearance of minute liquid spheres (globulites) , 4 which pass 
through several stages (margarites, longulites, etc.) before the crys- 
tal is formed. It seems possible that, under such enormous sub- 
division, cohesion retires into the background and surface tension 
assumes the chief role, so that the gold particles are rather to be 
compared to minute drops than to little crystals. 

Enough has been said to make clear the uncertainty which attaches 
to the attempt to classify colloid solutions according to the state of 
aggregation of the particles. A better classification is into reversible 
and irreversible colloids, according to the way in which the dissolved 
substance behaves when separated from the solution. Thus, when a 
gelatin solution is evaporated until it " sets " it is only necessary 
to warm the jelly with water to obtain it again in colloid solution. 
Gelatin is a typical reversible colloid. But when the gold is caused 
to separate from a gold sol — which can easily be brought about by 
adding any electrolyte to the sol — the gold will not again enter into 
colloidal solution. Shaking or warming with water gives a mere 

3 Thomas Graham introduced the term sol as an abbreviation for colloidal 
solution. 

4 Fink, " PoggendorfFs Annalen," vol. 46, p. 258 (1839) ; Schmidt, " Liebig's 
Annalen der Chemie," vol. 53, p. 171 (1845); Frankenheim, " PoggendorfFs 
Annalen," vol. in, p. i (i860). 



7 6 



Colloids and Crystals. 



I Am. Jour. Pharm. 
\ February, 1914. 



suspension, which settles at once. Gold is an irreversible colloid. 
The distinction is fundamental. Many organic colloids are reversible, 
while it is rather the habit of the inorganic colloids to behave in the 
irreversible way. 

IV. 

In order to prepare a sol containing an irreversible colloid all 
that is necessary is to reduce the solid to extreme subdivision in a 
liquid in which it is insoluble. The electric arc furnishes a rapid 
and simple method. 5 Two gold wires about 2 mm. thick are con- 
nected with a 220-volt circuit and brought together under distilled 
water. A no-volt circuit can be used, but more patience is required. 
Sols of platinum, silver, copper, and other metals can be made in the 
same way. By related electrical methods, using such liquids as pen- 
tane and anhydrous ether, Svedberg 6 obtained sols of all five of the 
alkali metals. The colors of the sols agreed with those of the vapors 
of the corresponding metals. 

Chemical reduction of a salt of a metal furnishes another method 
which has been largely employed by Zsigmondy 7 and other investi- 
gators. For instance, a very dilute solution of auric chloride is mixed 
with such reducing agents as formaldehyde, hydroxylamine or an 
ethereal solution of phosphorus. The gold sols obtained in this way 
are usually red by transmitted light, the particles being bright green 
and very much smaller than in the sols obtained by the electrical 
method. 

By various chemical methods, which lack of space forbids us .to 
discuss, sols of sulphides (CdS, As 2 S ;! , Sb 2 S 3 , etc.) and oxides 
(Fe 2 3 , A1 2 ;! ) can be obtained. The sol of aluminum oxide is im- 
portant on account of its connection with dyeing and mordanting. 
The formation of the blood-red sol of ferric oxide by adding a con- 
centrated solution of ferric chloride to about 50 volumes of boiling 
distilled water is a simple and beautiful lecture experiment. 

In making colloidal solutions of salts, the essential thing is to 
mix dilute solutions of the precipitants, using a liquid in which the 



5 Bredig, Zcitschrift fur angeivandte Chemie, 1898, p. 951. For a full 
account of Bredig's work with the platinum sol see Zcitschrift fur physikal- 
ischc Chcmic, vol. 31, pp. 258-353 (1899). 

6 Bcrichtc dcr dcutschcn chcmischen Gcsellschaft, vol. 38, p. 3616 (1905). 

7 See his monograph, " Zur Erkentniss der Kolloide " (Jena, 1905), which 
has been translated by Jerome Alexander. 



Am. Jour. Pharm. ) 
February, 1914. / 



Colloids and Crystals. 



77 



insolubility of the product is as complete as possible. Thus, in mixing 
very dilute solutions of sodium sulphate and barium chloride, a crys- 
talline precipitate is usually obtained. The reason is that barium 
sulphate possesses a very slight but real solubility in water. Hence 
the liquid in contact with the particles first formed contains enough 
barium sulphate to nourish their growth and allow them to develop 
to crystals. If alcohol is added to the sulphate, before the barium 
chloride is introduced, the solubility of the barium sulphate is greatly 
reduced, and it is obtained in colloidal solution without difficulty. 

In the same way, if we mix water solutions of sodium hydroxide 
and of hydrochloric acid we obtain merely an ordinary solution of 
common salt. But if salt is produced by a reaction between organic 
compounds in a liquid in which the sodium chloride is insoluble, then 
a colloidal solution is obtained. For instance, when chlor-acetic ester 
interacts with sodio-malonic ester a grayish opalescent sol of sodium 
chloride in ethenyl tri-carboxylic ester results : CHX1 COOC 2 H 5 -f- 
CHNa(COOC 2 H 5 ) 2 = CH 2 (COOC 2 B 5 ) — CH(COOC 2 H,) 2 + 
NaCl. At low temperatures, in such liquids as toluene and chloro- 
form, even ice has been obtained in colloidal solution. 

V. 

The most striking property of the reversible colloids is that they 
are able to communicate their reversibility to the irreversible ones. 
Thus, if a trace of gelatin is added to a gold solution, the gold 
becomes much more difficult to coagulate by electrolytes, and when 
coagulated it can be dispersed again by merely warming with water. 
This curious protective action is exerted, in greatly varying degree, 
by most reversible colloids. Direct study of the phenomenon with 
the ultra-microscope shows that the view frequently expressed that 
the gelatin envelops or forms a film around the gold particles is 
incorrect. What actually happens seems to be a direct combination 
between gelatin particles and gold particles, which then pass through 
the reversible changes together. 

Protective colloids enjoy a wide practical application. In the 
manufacture of photographic films the gelatin retards the crystalliza- 
tion of the silver bromide. Ink often contains a colloid which pre- 
vents the pigment from settling. The lubricant " aqua dag " put in 
the market by the Acheson Company consists of finely-divided arti- 
ficial graphite, held up by a protective colloid. Clay is made plastic 



78 



Colloids and Crystals. 



j Am. jour, Pharth. 
\ February, 1914. 



for the potter by an empirical process which involves the action of 
protective colloids derived from decaying vegetable matter. The 
addition of gelatin in making ice cream depends upon its protective 
action in preventing the growth of ice crystals, which would make 
the product " gritty." Without doubt protective action plays an 
important role in the cleansing action of soap. This has been 
made clear by some recent experiments of Spring. 8 Lampblack, 
freed from oil by long washing with alcohol, ether, and benzene, 
forms a rather stable suspension in water, but the lampblack is de- 
tained by a paper filter. If the filter is now reversed, so that the 
blackened surface is outward, and water poured through it, the lamp- 
black is not removed, but a dilute soap solution removes the coating 
and cleanses the filter at once. Finally, lampblack suspended — or col- 
loidally dissolved — in soap solution, passes through a filter unchanged. 
It is of much practical interest that there is a well-marked optimum 
in the concentration of the soap required to protect the lampblack. 
A one per cent, soap solution is the most efficient. In two per cent, 
soap solution lampblack sinks about as rapidly as in pure water. 

VI. 

We have already considered the probable actual condition of the 
particles in a colloidal solution and have concluded that, for the 
present, no very definite information is obtainable about the matter. 
We must now return, for a moment, to the subject in order to allude 
to the thesis so brilliantly advocated by van Weimarn, the Russian 
investigator, who holds that the particles are of necessity minute 
crystals and that there is, in fact, no such thing as amorphous matter. 
He even goes so far as to state that substances like air and water 
are in a " dynamic crypto-crystalline condition," though I have been 
unable to understand what he means by this statement. 

Briefly, the evidence that van Weimarn adduces to the support 
of his hypothesis is : 

(1) That colloid particles will grow to crystals if provided with 
the proper nourishment, namely, a dilute solution of the same 
substance. 

(2) That colloid particles are capable, when introduced into 

8 Kolloid Zeitschrift, vol. 4, p. 161 (1909); Kolloid Zeitschrift, vol. 6, 
pp. 11, 109, 164 (1910). 



Am. Jour. Pharm. ) 
February, 1914. J 



Colloids and Crystals. 



79 



a supersaturated solution of the same substance, of discharging the 
supersaturation and inducing the formation of crystals. 

Those who desire to follow this matter further should read 
van Weimarn's little book, " Grundziige der Dispersoidchemie," 
after which they will find themselves very much interested, but 
somewhat unconvinced. Let me hasten to add that I have not the 
least desire to undervalue the brilliant experimental work of the Rus- 
sian chemist. It is, in fact, precisely by the conception of more 
or less daring hypotheses, and the working out of their consequences, 
that our science achieves its endless victory over the nescience 
about us. 

VII. 

We have seen that the wave-lengths of the visible radiations are 
comprised between 0.4 /x and 0.7 With objects much smaller, the 
ordinary microscopic method ceases to be applicable. Using ultra- 
violet radiation for illumination, quartz lenses in the microscope, and 
receiving the image with the photographic plate instead of the eye, 
it is possible to advance a step further in the domain of the infini- 
tesimal, but only a step, and there are obvious objections to the 
proceeding. Since some of the particles in colloidal solutions are 
only 0.006 ^ in diameter, we can never hope to see them as little 
bodies subtending a visual angle. The ultra-microscope — -the power- 
ful instrument of investigation to' which most of our knowledge of 
colloid systems is due — renounces this idea and makes the particles 
visible merely as glittering points on a black background. The sol 
is placed in a small rectangular glass trough and a horizontal beam 
of arc light or sunlight focussed in it. The microscope is placed 
vertically above the trough. It will at once be seen that there are two 
fundamental things about the instrument : to< provide intense illumina- 
tion, and to make sure that no light enters the microscope except the 
rays which emanate from the particles. The principle is simple, but 
the system of diaphragms and lenses needed to secure the second 
object makes the ultra-microscope an elaborate and expensive instru- 
ment in practice. 

Cotton and Mouton 9 achieve the same end in a different way. 
The illumination (arc or sunlight) is thrown up from below by a 
paraboloid reflector so ground that all rays, except those diffracted 



Compt. Rendus, vol. 136, p. 1657 (1903). 



So 



Colloids and Crystals. 



{Am. Jour. Pharm. 
February, 1914. 



by the particles, are totally reflected from the cover-glass over the sol. 
This instrument is simple, easily adjusted and cheap. It is made 
commercially by the firm of Zeiss. It would seem to be admirably 
adapted to school purposes. In fact, after a look into the ultra- 
microscope, the study of the molecular topics ceases to be drudgery 
and becomes a positive intellectual need. 

VIII. 

Even a brief glance at the subject of colloid systems must at least 
mention the classic work of Perrin 10 on the distribution of the par- 
ticles in suspensions of gamboge and mastic. He succeeded, by an 
ingenious and simple method, in preparing emulsions of gamboge 
in water in which the spherical yellow granules were all of the same 
diameter. If we consider a mass of such a liquid in a tube, it is clear 
that the granules, if at rest, would, since they are denser than water, 
all fall to the bottom. The fact that they remain suspended is due to 
their movement. In other words, the state of things is the same as 
in the earth's atmosphere, and just as the molecules are more crowded 
near the earth's surface, so the granules of gamboge must be more 
numerous near the bottom of the liquid than in the upper layers. 
Perrin verified this prediction by direct counting of the granules 
under the microscope. The barometric formula which describes the 
progressive rarefaction of air with increasing height also describes 
the distribution of the granules in Perrin's uniform emulsions. The 
only difference is that, while the aviator must ascend six kilometres 
in order to reach air half as dense as at sea level, the same effect is 
produced, in Perrin's emulsion, by an ascent of o.i millimetre. 

That the mean energy of rotation of a molecule must be equal to 
its mean energy of translation is one of the chief propositions of the 
kinetic theory. Perrin has proved this by direct measurement of the 
rotation of granules under the microscope. For this purpose, large 
granules (15 /x) of mastic were employed. These are far too heavy 
to remain suspended in water, so a solution of urea was used. For- 
tunately, the granules contain little inclusions which make it possible 
to measure their rotation. 



10 Annates de Chimie et de Physique, 3d series, vol. 18, p. 5 (1909). There 
is a German translation by Donau in Kolloidchemische Beihefte, vol. 1, p. 1 
(1910). An English translation by Soddy has appeared in book form under 
the title " The Brownian Movement and Molecular Reality." 



Am. Jour. Pharm. ) 
February, 1914. J 



The Starch Grain. 



81 



These are only two> of many fundamental results contained in this 
wonderful memoir. Van't HofT extended the gas laws to solutions. 
Perrin has now proved them to be valid for systems in which the 
moving particles are visible realities. Let us end by quoting one of 
the sentences of his conclusion : 

" ha decouverte de telles relations marque le point ou s'eUve, 
dans notre conscience scientiUque, la realite moleculaire sousjacente." 



THE INFLUENCE OF HEAT AND CHEMICALS ON THE 
STARCH GRAIN. 1 
By Henry Kraemer. 

In presenting some of the most recent observations on the starch 
grain, it may be well to consider for a moment the nature and 
origin of starch. In a way starch is one of the most remarkable 
substances produced by the plant. It is the first visible product 
formed by the chloroplastid, or chlorophyll bodies, from the inor- 
ganic substances, carbon dioxide and water. Inasmuch as sunlight 
seems to be necessary to bring about this transformation the process 
is looked upon as one which involves the converting of the sun's 
energy into vital energy. 

The substance thus formed by the chloroplastid through the 
influence of sunlight, in the leaves and other green parts of plants, 
is known as " assimilation starch," and serves subsequently not 
only as a food for the plant itself but is also the source of the 
energy of the animal world. Assimilation starch is not stored in 
the cells where it is manufactured, but each night through the 
influence of the plant ferments the starch formed during the day 
is converted into a soluble form, and transported to various other 
parts of the plant. In some cases this soluble starch is tem- 
porarily stored in the cells of the pith, medullary rays, or bark, 
and has received the name of " depot starch." While some of 
the soluble carbohydrate is converted into fixed oils and other 
substances, a considerable portion of it is carried to some reserve 
organ, as a root, tuber, rhizome, or seed, and under the influ- 
ence of a plastid similar to the chloroplastid, converted into a 
stable form, known as reserve starch. 

1 Reprinted from Original Communications, Eighth International Con- 
gress of Applied Chemistry. Vol. XVII — Page 31. 



82 



The Starch Grain. 



J Am. Jour. Pharm. 
i February, 1914. 



Ihis is the product with which we are specially concerned in 
the present article. Hereto t ore, the minute study of the starch 
grain, particularly of its structure, has been of scientific interest 
only, but with the application of scientific methods in nearly every 
department of industry, it is coming to have a practical application. 

The commercial reserve starches are derived from various 
plants, and not only enter largely into food products but are also 
used for a variety of technical purposes. The grains of the re- 
serve starches have a number of characteristic features. They 
vary in size, in shape, in internal structure, and also to a con- 
siderable extent in composition. The variation in composition is 
shown by the use of aniline stain and also by the use of iodine. 
By the treatment of starch with iodine solution, we may distinguish 
three kinds of reserve starch: (i) one which is colored deep blue, 
as potato and maranta; (2) one which is colored somewhat purplish, 
changing to cinnamon-brown, as corn and wheat; and (3) one 
which is colored brownish-red, as in the amylo-dextrin starches 
of comfrey and a few other plants. 

The shape of the grains varies from polygonal to ellipsoidal, 
the shape being influenced by the number of grains in a cell. Under 
the micro-polariscope the grains are seen to be anisotropic, the 
polarization effects differing with the grains of the different classes. 
Polarizing effects are usually produced by crystals, but may be 
produced by substances in a condition of tension, as minute globules 
of glass. It should also be stated that cell walls have this same 
property of double refraction, and it is very likely that the sub- 
stances in the starch grains, as well as in the cell wall, are 
crystalloidal and arranged in spherite aggregates, resembling those 
of inulin, a product closely resembling starch. 

The theories which have been advanced regarding the struc- 
ture of the starch grain, have been largely based on studies of 
the potato starch grain. It was originally thought to be in the 
nature of a globule filled with a fluid. Fritzche, Schleiden and 
others considered it to be made up of more or less concentric 
layers formed around a central or excentral point. While it may 
be true, as pointed out by Naegeli, that many of the reserve and 
glucose starch grains arise free in the cell, the view of Schimper 
that starch grains always develop within plastids, is generally 
accepted at the present time. 

The internal structure of the starch grain is shown in several 



Am. jour. Piiarm. \ 
February, 1914. J 



The Starch Grain. 



83 



ways. When starch is treated with certain chemicals, or heated 
with water alone to a temperature of 6o° C, the grains show a 
series of successive changes. First, the lamellae or layers become 
more distinct, and the layers appear to be made up of parallel 
crystal-like particles, these latter being more numerous in suc- 
cessive alternate lamellae. Then as the grain swells clefts which 
radiate from the centre are formed. Later the centre of the grain 
becomes hollow, and when the grain has swollen to about four 
times its original size the outer membrane breaks and the con- 
tents are gradually dissolved. 

Some striking effects are also produced when starch is carefully 
treated with aniline dyes. The point of origin of growth and the 
successive layers alternating with it take up the stains, thus again 
showing the distinct character of the two kinds of lamellae making 
up the grains. When plant material containing mucilage is treated 
with aniline stains, the stain is taken up only by the cells containing 
mucilage, and this indicates that the lamellae in a starch grain 
which take up the stains are composed chiefly of colloidal sub- 
stances. From these observations it is apparent that the grains 
of certain of the starches, as the potato, if not of all the lamellated 
starch grains, are made up of two kinds of lamellae, one rich in 
colloids and one rich in crystalloids. The presence of two kinds of 
lamellae, at least in certain of the starch grains, and their difference 
of composition are further shown by the use of a weak solution 
of iodine, the so-called crystalloidal layers or lamellae taking up the 
iodine and becoming blue. 2 

Recently I have been conducting some experiments to deter- 
mine further the effects of heat upon the structure of the starch 
grain. When starch alone is heated to between 45 ° and 50 C. from 
15 to 30 minutes, the lamellae and the crystalloidal structure of the 
grains are brought out. The grain is so resistent that the inner 
structure does not appear to be lost until a temperature of over 
125 C. is attained. Between 140 and 160 C. the polarization effects 
of the grains become faint, except in the case of potato starch, 
which now in addition gives chromatic effects. At 240 C. all of the 
grains are disintegrated except those of corn starch, the individual 
grains of which are of a brownish-yellow color and not perceptibly 



2 Kraemer, Bot. Gazette, Vol. XXXIV, Nov., 1902 ; Ibid., Vol. XL, Oct., 
1905; reprinted in Amer. Jour. Pharm., Vol. 79, 1907, pp. 217-229; 412-418. 



8 4 



The Starch Grain. 



{ Am. Jour. Pharm. 
V February, 1914. 



swollen. Besides the entire mass is more or less granular, while 
in the case of the other starches examined the charred mass is in 
a puffed condition. 

The effects produced when starch is heated in the presence 
of a fixed oil, as almond oil, are of special interest. The inner 
structure of the starch grain is not usually apparent when it is 
mounted in a fixed oil, unless the starch has been previously heated 
to a temperature of from 8o° to 160 C. When, however, a mixture 
of starch and oil is heated as high as i8'o C. the grains still polarize 
light, which shows that the structure has not been altered. In 
other words the effects of heat on the grain are more or less 
neutralized by the presence of the oil. On heating the mixture up 
to 250 C. most of the grains still show their individual character, 
but no longer polarize light. They are but slightly swollen, and 
in the case of cassava and corn starch a central differential area 
occupies from one-half to nine-tenths of the original area of the 
grain. 

It may be worth while to state that when starch and water 
in the proportion of 2 gm. of the former to 100 c.c. of the latter, 
are heated together at a temperature of between 90 and ioo° C. 
in a steam sterilizer seven or eight hours a day for a long period, 
even extending to months, dextrinization of the starch does not 
take place, that is, the solution still gives a blue color with iodine. 
Even though the operation be conducted in an autoclave under 
a pressure of 20 pounds for about ten hours, dextrinization is 
not effected. If, however, 1 c.c. of N/HC1 be added to 100 c.c. 
of water and this heated for five hours with 1 gm. of starch, the 
resulting solution is colored red with iodine. When the amount 
of the acid is reduced to .2 c.c. and the mixture heated under 
a pressure up to 12 pounds for one hour, cassava, corn, maranta 
and potato starch solutions give a deep blue color with iodine, 
while a solution of wheat starch gives a deep purple color with 
iodine. If the heat be continued an hour longer, wheat starch 
gives a purplish-red color, cassava a deep wine color, maranta 
and potato a light purple, while corn still gives a blue reaction 
with iodine. 

These observations may be summarized as follows : 
1. The starch grain consists of two nearly related substances: 
(a) a colloidal or mucilage-like substance which takes up aniline 



Am. Jour. Pharm. ) 
February, 1914. / 



Book Reviews. 



85 



dyes, and (b) a crystalloidal or crystal-like material giving a blue 
color with iodine. 

2. The starch grain is made up of concentric layers, one series 
of which contains a large proportion of crystalloids, while the 
alternate layers are composed mostly of colloids. 

3. The polarization effects produced by starch are probably to 
be attributed to the crystalloidal character of the grains. 

4. The starch grains retain their polarizing properties even when 
heated up to a temperature of 180 C, which seems very remarkable 
indeed. 

5. At the higher temperatures the potato starch grains give 
chromatic effects in addition, similar to those when a selenite 
plate is used. 

6. While heating the starch grains in water rapidly changes the 
structure of the grain, it is only by the addition of chemicals or 
ferments that dextrinization is brought about. 



BOOK REVIEWS. 

Semi-Annual Report on Essential Oils, Synthetic Per- 
fumes, &c. Published by Schimmel & Co. (Fritzsche Brothers), 
Miltitz near Leipzig. London, New York. October, 1913. 

In the introduction to this report an admirable resume is given 
of conditions, both favorable and adverse, which affected business 
in the last year and particularly as to commodities handled by this 
firm. 

As is known to well-informed pharmacists, the practice of 
sophistication is found in many branches of business but in none 
so much as in the essential oil industry. In fact, one is almost led 
to believe that adulteration of oils and perfumes is an industry in 
itself. Upward movement of prices is the dominant cause for this, 
and, as is always the way, the forces of evil and dishonesty are up 
and doing, and " the practice of adulteration is assuming dimen- 
sions, and is pursued with refinements of ingenuity that baffle de- 
scription." So cleverly are adulterants selected and manipulated 
that the constants of an adulterated oil are kept within the right 
limits of value and only a most thorough examination will show the 
true state of affairs. Artificial esters play an important part in this 
nefarious work ; for instance, when added to oils such as lavender 



86 



Book Reviews. 



f Am. Jour. Pharm. 
\ February, 1914. 



and bergamot, they give " to them the appearance of containing far 
more linalyl acetate than the oils possess in reality." 

In this report the statement is made that there are firms who do 
not hesitate to offer such esters openly for purposes of adulteration. 
Furthermore, it is stated that one firm made such an offer to the 
Schimmel people in writing who publish this communication in the 
original language and a translation of which follows : 

Gentlemen : 

For some years past we have been in the habit of supplying to 
lavender growers a product called " Ether L." 

The advantage of this article is that it simulates in a perfect 
manner essential oil of lavender, and we have judged it opportune 
to forward you to-day a sample of it by post. The price is 12.50 
francs per kilo delivered at your works. 

If this product should interest you by any chance, please let us 
know what quantities of it you would be able to use annually. 

Hoping to hear from you we are, &c, 

N. V. Polak & Schwarz's, 

Essence Fabrieken, 
Zaandam ( Holland ) . 
P. S. — Our Ether L. is pure and contains 100 p. c< 
Subsequent examination of this product showed that instead of 
being 100 per cent, it revealed a percentage of 86. The presence of 
this ester in lavender oil would not prove difficult of detection. 

The high price of menthol also proved a stimulus to those of dis- 
honest tendencies. Two samples examined showed 100 per cent, 
adulteration. Both were acetanilid, one scented with menthol and 
the other with peppermint oil. Under the name Mentholin there is 
being offered to the trade a substitute for menthol made by a firm 
in Prague which proved to be 80 per cent, acetanilid and oily 
menthol. 

This report consists of 151 pages of interesting matter, the 
greater part of which is devoted to commercial notes and scientific 
information pertaining to essential oils ; practically every oil used in 
pharmacy and in the manufacture of perfumery is touched upon as 
to source of production, supply, and conditions, favorable and other- 
wise, which may have had some influence on quality or lack of 
quality. 

Considerable attention is given to recent scientific research in 



Am. Jour. Pharm. ) 
February, 1914. j 



Book Reviews. 



87 



the field of essential oils. Abstracts of reports on experimental cul- 
tivation of medicinal plants are given, a field of endeavor which 
must be nurtured if the supply of drugs is to keep pace with the 
demand. 

Among the pages of this report are several excellent pictures 
illustrative of the essential oil industry. One is a particularly strik- 
ing view, in color, of the Miltitz rose-fields at harvest time. 

After reading over this report and digesting the information 
given, one cannot help but feel that in the examination of an oil 
(say oil of rose) and in which the other constants are normal — a 
remarkably high ester value should be regarded with suspicion ! 

British Pharmaceutical Conference. A Presidential 
Survey 1863 to 1913. Being a sketch of the origin and progress 
•of the conference prepared on the occasion of the celebration of its 
jubilee in London, July 21 to 25, 1913. The Chemist and Druggist, 
42 Cannon Street, London. 

This handy little volume of 96 pages contains concise but inter- 
esting biographies of the various men who have been honored by the 
presidency of the British Pharmaceutical Conference. 

In the fifty years of its existence the Conference has been guided 
by thirty-three presidents, all men of ability and some of rare scien- 
tific attainments. Among the list of names two stand out in bold 
relief — Hanbury and Attfield. These two names are probably more 
familiar to workers in pharmacy in this country than any other two 
from other lands. Hanbury won an enviable position in the world 
of science by his work as a pharmacognocist. He will also be remem- 
bered as the donor of the Hanbury Medal. This is only given to 
men who have done something and our own Professor Maisch was 
the first American to> receive this signal honor. And Attfield, we 
think few American students are unfamiliar with the book on chem- 
istry bearing that name, with its many chemical experiments which 
the student is advised to perform. He impressed on the student 
the fact that the way to study chemistry was to work at it. 

John K. Thum. 

Payne's Dictionary of Pharmacy. By George F. Payne, 
Ph.G., M.D., F.C.S. Published by G. F. Payne, Atlanta, Ga. 

Lack of space forbids us to give the full title given by the author 
to this little handbook of pharmaceutical facts. For the same 



88 



Book Reviews. 



f Am. Jour. Pharm. 
\ February, 1914. 



reason we are compelled to omit mention of the numerous offices 
and honors the distinguished writer has been honored with and 
which he mentions on page one. It suffices to say that he is " an 
active pharmacist for 51 years"; that the little volume is copy- 
righted, and all rights are reserved, whatever that may mean. 

We have been rather hopeful that the day of cramming books 
was over, but this short-cut to the study of pharmacy and allied 
branches seems like evidence to the contrary. 

The study of a science and art like pharmacy by the " absorp- 
tion " of isolated facts is a survival of the day when the unschooled 
errand boy of the retail drug store developed into a clerk and squeezed 
through a board of pharmacy examination by heroically attempting 
to memorize the dispensatory. In the past, board of pharmacy ex- 
aminations consisted very much of " catch " questions and a student 
expected them and prepared for them ; if he answered them correctly 
the board assumed that he was fit to practise pharmacy ; all of which 
was not conducive to the best interests of the public and cer- 
tainly lowered the level of the profession. Indeed, the inefficiency 
of many pharmacists, who must, because of such inefficiency, depend 
upon manufacturing houses for many pharmaceuticals that they 
should make themselves, can be traced to this method of education 
or lack of education in their chosen profession. 

Happily, in the larger centres of our country there is beginning 
to manifest itself by the public a demand for a higher type of man 
for the professions, ours included. And this demand is being met 
and complied with by the better class of schools with more stringent 
requirements as to preliminary education and a broadening of the 
curriculum. This is as it should be, and in the evolution of things 
schools of other centres must do likewise or cease to exist. 

John K. Thum. 

Materia Medica, Pharmacology, Therapeutics, Prescrip- 
tion Writing, for Students and Practitioners. By Walter A. 
Bastedo, Associate in Pharmacology and Therapeutics at Columbia 
University, etc. 

This book, which is from the press of the W. B. Saunders Co., 
is a medium 8vo. in size, of 602 pages, price $3.50 net. It is an ex- 
cellent specimen of the book-making art, the binding and paper 
being excellent, the type clear and distinct. 



Am. Jour. Pharm. ) 

February, 1914. J 



Book Reviews. 



8 9 



The work is original in many respects, not following the beaten 
path, and has in it much to commend. 

It is divided into three parts, Part I being largely by way of in- 
troduction. Among some of the subjects considered in this divi- 
sion are : Pharmaceutical preparations ; Weights and measures ; 
Active principles ; The Pharmacopoeia ; Dosage, Administration of 
medicines, etc. 

Part II treats of materia medica proper. Many of the classifi- 
cations are different from other books on this subject, one of them 
being Sweetening Agents, which includes saccharin, which he 
states " has been much employed in canning foods, as it is slightly 
antiseptic and obviates the use of the highly fermentable sugar." 
This seems to be flying directly in the face of Dr. Wiley. The Anti- 
Bitters are claimed to abolish the appreciation of bitter tastes ; these 
include yerba santa and gymnemic acid. The list of cathartics in- 
clude those which act by " selective affinity," as physostigmine, which 
stimulates the ends of the vagus nerves of the intestines. A new 
classification is given to the Antispasmodics, they being called the 
Antihysterics. 

The classification of the Antipyretics is somewhat original. We 
have the analgesic antipyretics, such as antipyrin, the antimalarial 
antipyretics, such as cinchona ; and the antirheumatic antipyretics, 
such as salicylic acid. 

The article on the thyroid gland is interesting and of value, a new 
classification being called the Antithyroid preparations, designed to 
overcome undue activity of the thyroid gland, the remedies included 
under this head being Beebe's serum; Antithyroidin (Moebius), and 
Thyroidectin. Antithyroidin is the blood serum obtained from sheep 
whose thyroid glands have been removed, at least six weeks before. 

The therapeutic classification of the Disinfectants is also original 
and valuable. It includes I, The general disinfectants and deo- 
dorizers ; II, The preservatives ; III, Disinfectants for surgical sup- 
plies ; IV, Disinfectants for local use about the body ; V, Disinfect- 
ants to be given by the mouth. The important drugs of the materia 
medica are treated of at considerable length, digitalis having 42 
pages assigned to it, and epinephrine (adrenalin) ten pages. In 
the article on digitalis, it is stated that " digitalis contains digitonin, a 
saponin body which foams with water and possesses the peculiar 
property of holding the otherwise insoluble active principles in solu- 
tion in water. It is on account of this that infusion of digitalis, an 



go 



Book Reviews. 



f Am. Jour. Pharm. 
[ February, 1914. 



aqueous preparation, represents the activity of the drug." While 
this is somewhat different from what we have heretofore believed, it 
does not justify the making of the infusion from a fluidextract, as 
digitonin is not soluble in an alcoholic menstruum, and such an infu- 
sion would not contain any digitonin, and the glucosides insoluble 
in water would not therefore be held in solution. 

The book is up-to-date in the introduction of new remedies, a 
few only being cited, such as Hormonal from the spleen of the 
rabbit, which is stated to be " of value in post-operative tympanites 
and obstinate chronic constipation." Oxyntin and Acidol are albu- 
minous forms of hydrochloric acid. The chapter on Hypnotics is of 
interest, especially the contrast between natural sleep and that in- 
duced by the aid of drugs. 

" The article on tobacco will be read with interest, as the author 
seems to think " that the demand for tobacco is not so much the 
physiological demand of the body for its dose of nicotine, as it is the 
psychic demand for the satisfaction of a habit." 

He thinks that pepsin " in almost all cases of digestive disturb- 
ance is a superfluous remedy," but that pancreatin is of greater 
value. In fact, he gives some remarkable instances of its effects in 
the case of arrested development, one of which was a boy who grew 
five inches in two years and gained twenty-two pounds. He is op- 
posed to the prescribing of mixtures of the digestive ferments to- 
gether, as frequently they destroy each other. Of aconite which 
has been the sheet anchor of Homeopathy for so many years, is 
asserted, " that in the light of recent research has doubtful thera- 
peutic value." Camphor cerate is not " camphor ice " as stated, the 
latter being the Compound cerate of the N. F. Jalap is said to 
contain 8 per cent, of resin, the amount should be given as 7 per 
cent. The doses as given in the work vary considerably from those 
of the pharmacopoeia. Under the head of reflex emetics, the dose of 
copper sulphate is stated as thirty grains, the pharmacopoeia gives 
it as four grains, that of tartar emetic as two grains, the official dose 
is y^t g. ; we have same unpleasant remembrances of the effects of a 
one-grain dose of tartar emetic. The dose of sparteine sulphate is 
given as one grain, which is probably nearer correct than the dose 
given in the Pharmacopoeia. The dose of all the mydriatic alkaloids 
(as atropine) and their salts is stated as the 1/150 grain, no varia- 
tion between them being given. 

Apomorphine hydrochloride is cited as being the only central 



rtSS,?™'} Philadelphia College of Pharmacy. 91 

(systemic) emetic, other authorities include tartar emetic, senega and 
squill. 

Part III is devoted to Prescription Writing, which the author 
states " is the dread of the young medical practitioner." This part, 
while brief, is quite practical, and may be of considerable value in 
starting the young practitioner aright, but what he should have to 
make him an expert in the art of prescription writing is a more ex- 
tensive practice while in college. Much of the fourth year in college 
could be devoted, directly or indirectly, to this work, and then the 
young physician would be able to use his knowledge of materia 
medica intelligently and practically. In conclusion, we would state 
that we have examined the book with much interest, and shall have 
pleasure and profit in consulting its pages in the future; it is well 
worthy of being added to every physician's library. 

C. B. Lowe, M.D. 



PHILADELPHIA COLLEGE OF PHARMACY. 
Minutes of the Quarterly Meeting. 

The quarterly meeting of the Philadelphia College of Pharmacy 
was held December 29th, 19 13, at 4 p.m., in the Library. The Presi- 
dent, Howard B. French, in the Chair. Sixteen members present. 
The minutes of the semi-annual meeting held September 29th were 
read and approved. The minutes of the Board of Trustees, for the 
meetings held September 2-16, October 7, and November 5, were 
read by the Registrar, J. S. Beetem, and approved. 

Acknowledgments of having received notice of their election to 
Honorary Membership were received from Doctors Carl L. Alsberg 
and A. L. Winton. 

The President reappointed the following as the Committee on 
Legislation : Warren H. Poley, Joseph P. Remington, Theodore 
Campbell, William E. Lee, William L. Cliflfe, Richard H. Lackey. 

C. A. Weidemann, M.D., 

Recording Secretary. 

Abstracts from the Minutes of the Board of Trustees. 



September 16th: Thirteen members present. The Committee 
on Property reported that the Library ceiling had been repaired, 
woodwork cleaned and varnished, new carpet (cork) put down, 



92 Philadelphia College of Pharmacy. {Veb™£,^™" 

and new chairs purchased. Also that the woodwork of the lower 
front of the College had been painted, that changes had been made 
in the lower Microscopical Laboratory, and that the Gymnasium 
had been put in first class condition. 

The Finance Committee approved the recommendation that 
Prof. Moerk engage the services of two student assistants and Prof. 
Kraemer one student assistant for the College term. 

The Committee on Appropriations approved the estimated 
amounts that would be required by the several committees and de- 
partments authorized to make expenditures. 

The Committee on Scholarships. — The Chair reported that owing 
to the absence of the Dean in Europe, it was necessary to act on the 
applications presented at the October meeting of the Board and 
suggested that the Assistant Dean be placed on the Scholarship 
Committee in the interim. It was so ordered. 

The Joint Committee on Instruction and Examination made a 
report relative to students taking the course in Bacteriology, which 
was adopted. 

The Committee on Examinations reported that John L. Bush, 
Harry C. Cowles, and Paul A. Kind, having complied with all th^ 
requirements, were recommended to receive the Certificate of Pro- 
ficiency in Chemistry ; and that Roy L. Clark having complied with 
all the requirements was recommended to receive the Certificate of 
Proficiency in Food and Drug Analysis. These recommendations 
were approved. 

The Committee on Announcement reported the regular issuance 
of the Bulletin. 

A letter was read from the Secretary of the State Pharmaceutical 
Board relative to the fact that the highest ratings of those who ha 1 
taken the June examinations had been bestowed upon two graduates 
of the Philadelphia College of Pharmacy. 

Mr. French referred to the honor conferred upon Dr. F. B. 
Power, a graduate of the College, who had been awarded the 
Hanbury Gold Medal, and he suggested that a letter of congratula- 
tion be sent Dr. Power. This met with hearty approval and the 
suggestion was adopted. 

An application for active membership was received and referred 
to the Committee on Membership. 

The Treasurer's Annual Report was received, and referred to 
the Committee on Accounts and Audit. 



A Sb™ary, P i h 9T'} Philadelphia College of Pharmacy. 93 

October 7th: Thirteen members present. A communication 
was received from the Recording Secretary of the College report- 
ing the election of E. M. Boring, Charles Leedom, and Theodore 
Campbell to membership in the Board of Trustees for the ensuing 
three years. 

The Committee on Property reported that the back hall and 
stairway had been painted and put in good condition. 

The Committee on Library reported that up to this time 5246 
books had been classified, accessioned and shelf -listed. 

Donations of books had been received from H. G. Kalmbach, 
Mrs. Wm. Mclntyre, Professor C. B. Lowe, Professor Henry 
Kraemer and the Surgeon's General Office. A number of books 
had been purchased. Fifty-two persons had used the Library. 

The Committee on Instruction reported that several students 
had removed conditions, and that several others still had con- 
ditions to be removed, and suggested rules to govern such cases in 
the future; also that Prof. Kraemer had selected Anton Hogstad, 
a third year student, as an assistant. 

The Chairman stated that Professor Roddy had requested 
Messrs. Mulford & Company and Parke, Davis & Company to pre- 
sent samples of Bacteriological products to his laboratory, with 
which request they had complied and new products would ac- 
cordingly be added. The thanks of the Board was conveyed to 
the donors. 

The Committee on Scholarships reported the names of twelve 
persons to whom scholarships had been awarded. 

Mr. Shoemaker read a communication from Prof. Kraemer 
to the Registrar relative to the fund started by the classes ending 
in 4 and 9, to the effect that the fund be placed in the hands of 
the Treasurer. The Treasurer suggested that the fund be one 
representing all graduates. Prof. Kraemer was requested to out- 
line the plan undertaken by the classes and to submit such out- 
lined plan at the next meeting of the Board. 

An application for Associate Membership was received and 
referred to the Committee on Membership. 

The Committee on Membership reported favorably on the ap- 
plication of George L. Sbntag, of Neillsville, Wisconsin, Class of 
1890. A ballot was taken and he was unanimously elected. 

November 5th: Thirteen members present. Committee on 
Library reported an additional number of books accessioned, classi- 
fied and shelf-listed and that a gift had been received from G. 
Mason Thompson. A number of books had been purchased. One 
hundred and forty-six persons had used the Library. 



94 Philadelphia College of Pharmacy. { VeJuarj/ifi 1 ' 

Committee on Instruction reported that the Sub-Committee on 
Special Lectures had secured outside talent to deliver nine special 
lectures during the College term. A wide range of subjects having 
been selected. Several joint meetings of the Committees on Instruc- 
tion and Examinations were held to formulate some system of 
grading or evaluation to be attached to the results of the examina- 
tions in the various branches of the College — such system that 
differentiates between the Major and Minor branches. After 
earnest consideration, a plan has been proposed by which each sub- 
ject of instruction will be given a rating corresponding with its 
importance. This plan will be put in force for the present year in 
order that its adaptability to the conditions now existing may be 
tested. 

The Secretary announced that he had received letters from the 
recipients of scholarships expressing their appreciation. 

The Chairman read a letter from Dr. F. B. Power expressing 
his appreciation of the good wishes and congratulations extended 
him by the College. The correspondence was directed to be pub- 
lished in the American Journal of Pharmacy. 

Philadelphia College of Pharmacy. 

September Twenty-third, 19 13. 

Dr. Frederick B. Power, 

Snow Hill, London, E. C, England. 

Dear Doctor : 

The news that the Committee on Hanbury Medal of the Pharma- 
ceutical Society of Great Britain had awarded you this year this 
coveted medal, has been received by the members of the Philadelphia 
College of Pharmacy with mingled feelings of pleasure and pride. 
It is now nearly forty years since your first scientific papers were 
published in our Journal and we appreciate that with the harvest 
of material that is yours, you still remember us. It is but natural 
on an occasion of this kind, being probably the proudest in your 
life, that we in offering you our felicitations and congratulations 
should remind you that the successive steps in your career since 
graduating from our College and working in its faculty, have been 
followed by us with increasing interest as year by year has passed. 
Rarely does it fall to the lot of any one man to accomplish so much, 
and it is even more unusual for him to receive while yet in his prime, 
the recognition he deserves for the days and nights of unremitting 



A reb^uaJy, P i h 9 a i4 m '} Philadelphia College of Pharmacy. 95 

toil with which he has applied himself to his chosen task. We trust 
that you may be spared many years to continue your studies, and it 
is our earnest desire that the harvest may satisfy your proudest hopes 
and highest expectations. We wish you health that you may work 
easily as well as effectively and enjoy the fruits of your labors. 

Very truly, 

Howard B. French, 

President. 

The Wellcome Chemical Research Laboratories, 
Frederick B. Power, Ph.D., LL.D., Director. 

6, King Street, Snow Hill, London, E. C. 

13 October, 1913. 

Howard B. French, Esq., 

President, Philadelphia College of Pharmacy, 
Philadelphia, Pa. 

Dear Mr. French : 

It has given me exceptional pleasure to receive your very kind 
letter of the 24th ultimo, and 1 desire to assure you of my deep 
appreciation of the cordial sentiments and good wishes therein 
expressed. 

The significance of the honor attending the award of the Han- 
bury Gold Medal has been greatly enhanced to me by the feeling 
that its bestowal has also afforded gratification and pleasure to so 
many of my esteemed friends across the sea. The occasion of its 
presentation on October 1st was a memorable one, and it was a 
great delight to me, as indeed to the entire assembly, that Professor 
Remington could be present and participate in the proceedings. His 
remarks in seconding a vote of thanks, proposed by Sir William 
Tilden, F.R.S., for my address, were most felicitous, and it was al- 
together a grand and happy day. 

I have been deeply touched by the expressions of interest 
manifested in my career by the Philadelphia College, which has 
indeed been to me a " kindly mother." I am grateful for the stimu- 
lus to scientific study which was first received as a student within 
its walls, and appreciate very highly the honors it has in later years 
conferred upon me. 

In heartily reciprocating your good wishes for health and hap- 
piness, believe me to be, 

Sincerely yours, 

Frederick B. Power. 



96 Philadelphia College of Pharmacy. { A febm^i^' 

The Committee on Membership reported favorably on the ap- 
plication of Otto Raubenheimer, of Brooklyn, N. Y., as an As- 
sociate Member. A ballot was taken and he was unanimously 
elected. 

PHARMACEUTICAL MEETINGS. 

The second Pharmaceutical meeting was held on Friday after- 
noon, November 14, Mr. Edward M. Boring presiding. 

Prof. Charles H. LaWall presented a paper on " Detection of 
Chicory in Decoctions of Chicory and Coffee " prepared in conjunc- 
tion with Mr. Leroy Forman. 

Mr. Boring then exhibited two specimens of Elixir of Iron, Qui- 
nine and Strychnine, made six months apart, their fine appearance 
being due to neutralization after the addition of the iron phosphate. 

Prof. Remington gave a delightful talk on " Some Pharmaceutical 
Celebrities I Have Met," in connection with which he showed a large 
number of slides including portraits and views in laboratories abroad 
and in manufacturing houses. 

OBITUARY. 

Evan Tyson Ellis was born in Philadelphia on August 10, 1826 
and died in the same city on October 11, 1913. He was the oldest 
alumnus and member of the Philadelphia College of Pharmacy, the 
last surviving charter member of the Philadelphia Photographic 
Society, and for many years a prominent figure in the wholesale drug 
circles of Philadelphia. 

Mr. Ellis came of sturdy Quaker stock, his father, Charles Ellis, 
being a well known Orthodox Quaker, a leading wholesale druggist 
and an official, in various capacities, of the Philadelphia College of 
Pharmacy for more than forty years. He received his education at 
Haverford College from which he was graduated with the class of 
1844 and was one of the oldest members of the Haverford College 
Alumni Association. He then studied pharmacy, attended the courses 
of instruction at the Philadelphia College of Pharmacy, graduating 
with the class of 1847. The subject of his thesis was " Extract of 
Valerian." 

After he was graduated, Mr. Ellis went into partnership with his 
father, Charles Ellis, in Philadelphia, and together they built up a 
large wholesale drug business, under the name of Charles Ellis, Son 
and Co. During the Civil War he served in the Hospital Department 
of the U. S. Army. 

J. W. England. 



the ameeica: 
JOURNAL OF PU^lM^y 

MARCH, 1914 Vir^ ^ y ^ ^ 

DISTRIBUTION OF ALKALOIDS IN THE,B^LAD©NNA} | 

PLANT.* V X^e^ <CJ 

By A. F. Sievers, Chemical Biologist, 
Office of Drug Plant Investigations; Bureau of Plant Industry. 

In connection with an investigation of the individual variation 
of the alkaloidal content of belladonna plants, it was desirable to 
determine the relative distribution of the alkaloids in the plant. In 
this article are presented the results of a complete, detailed examina- 
tion of a number of such individual plants. The conclusions that may 
be drawn from these results are interesting in that they indicate a 
number of facts concerning the relative therapeutic value of various 
parts of the plant which may be of economic significance. Further- 
more, a definite knowledge of such a distribution may eventually 
add to our information concerning the role of the alkaloids in the 
physiological processes of the plant. 

In determining the alkaloids it was frequently necessary to assay 
very small samples. The method employed was that of the U. S. 
Pharmacopoeia with some modifications of the technique to make 
the process applicable to small samples. These modifications have 
been described in some previous articles. 1 Analyses were made of 
first and third year plants. 

Third- Year Plants. 

The analyses of the third-year plants were made in June, when 
they were in full bloom. Owing to the fact that most of these 
were reserved for other work, only four individual plants could be 



* Published by permission of the Secretary of Agriculture. 
1 Merck's Report, August, 1910, p. 215; Journal of the American Pharma- 
ceutical Assn., March, 1912, p. 199. 

(97) 



9 8 



Alkaloids in Belladonna Plant. 



J Am. Jour. Pharm. 
X March, 1914. 



secured for the experiment, but these four were typical of the 
entire plot. 

The green or aerial portion of each plant was separated into the 
following parts: (i) Flowers, (2) flowering tops, (3) small and 
large leaves, and (4) small and large stems. All the parts were im- 
mediately weighed so that the percentage of moisture could be de- 
termined. The flowers included only the open flowers. The flower- 
ing tops consisted of the tops of the branches, including about three 
or four inches of the young stems and the small and young leaves 
and flower buds. The small leaves were mostly of the younger 
growth, located largely near the upper part of the plant; a few, 
however, growing at the juncture of the old leaves and the stems. 
The large leaves were picked close to the stem, and the petioles 
at the base of the leaves were removed and kept separate. The large 
stems were separated from the small ones, the latter including 
those above the point where the large stem forks. The small stems 
as a rule were quite small and tender, averaging about a quarter of 
an inch in diameter. The large stems were split, the thin bark 
peeled off, and the pith, which constitutes the bulk of the interior 
of the stem, was scraped out. Each part was weighed separately. 

The roots were carefully dug out and thoroughly washed to re- 
move all dirt. The small roots, which consisted mainly of the young 
slender ends of the tap roots and secondary fibrous roots, were then 
separated from the large ones. The large roots, or thick tap roots, 
were separated into two parts, the wood and the bark. 

After being thoroughly air-dried, all parts of the plants were 
dried to constant weight in a hot-air oven at a maximum temperature 
of 60 degrees C. The alkaloids were determined by the method de- 
scribed, and the results of the analysis of each of the four plants 
are shown in Table I, which is summarized at the close, in order 
to compare the percentages of alkaloids in the several parts of the 
individual plants. 

First- Year Plants. 

There were six of the first-year plants, and these were analyzed 
in September, when the flowering was over and all but a few of 
the berries were ripe. The serial portion of each plant was separated 
into the following parts: (1) Small and large leaves, (2) young 
sprouts, (3) fruit, (4) small and large stems. The fruits or berries 
were picked with the stem and calyx attached, the latter being after- 



Alkaloids in Belladonna Plant. 99 
Table I. 



A nalyses of Four Typical Third-year Belladonna Plants. 



Plant and part 


Weight (grams) 


Moist- 
ure 
per 

cent. 


Per 
cent, of 
entire 
plant 


Alkaloids 


Green 


Dry 


Grams 


Per 
cent. 


Percentage 
of quantity 

of alka- 
loids in the 
plant 


Plant No. 1. 

Flowers 

Flowering tops . 

Leaves : 

Small 

Large : 

Without petioles . 

Petioles 

Entire 1 arge 
leaves 

Total 

Stems: 

Small 

Large : 

Pith 

Bark 

Wood 

Entire large 

Total 

Roots: 

Small 

Large : 

Wood 

Bark 

Entire large 
roots 

Total 

Entire plant 


34-15 
194.20 


5-75 
31-94 


83-I7 
83-57 


2.14 

11 .86 


O.O255 
•2753 


0-445 
.862 


2 .27 
24.42 


40.36 

187.44 
28.94 

216.38 


7-55 

31.04 
2.89 

33-93 


82.68 

83-42 
9O.OO 

84.3O 


2.81 

n.56 
1.07 

12 .60 


.0512 

"73 
.OIIO 

.1283 


.679 

•378 
■381 

.378 


4-54 

10 .40 
•97 

11-37 


256.74 


41.48 


83.70 


I5-70 


-1795 


•432 


15.90 


161.65 

141 .80 
95.20 
113 .00 

350 .00 


20.33 

10 .00 
10.76 
27.81 

4° -57 


87.40 
92.95 

87-93 
75-45 

86.10 


7-55 

3-71 
3-99 
10.33 

18 .04 


.0896 

•0337 
.0131 
.0292 

.0760 


.441 

-337 
.128 
-105 

-156 


7-93 

2.98 
1 .16 
2-59 

6 -73 


51165 


68.90 


86.58 


25-59 


.1656 .237 


14 .66 


85 -95 

473-30 
271 .70 

750.00 


13-81 

64-35 
42.95 

107 .30 


83 .92 

86.42 
84.20 

85.60 


5 • 1 3 

23.90 
15-95 

39.88 


.0701 

.2786 
•1331 

4II7 


.508 

•433 
.310 

.383 


6 .22 

24.72 
11 .81 

36.53 


835-95 


121 .21 


85.40 


45-01 


.4818 


.398 


42-75 


1,832.69 

1 


269 .28 


| 85.31 




I . 1277 


.418 

1 


100. 








ioo Alkaloids in Belladonna Plant. { Al Q ^/ r ™ r - 



Table I. — Continued. 



Analyses of Four Typical Third-year Belladonna Plants. 





Weight (grams) 






Alkaloids 


Plant and part 


Green 


Dry 


Moist- 

per 
cent. 


Per 
cent, of 
entire 
plant 


Grams 


Per 
cent. 


Percentage 
of quantity 

of alka- 
loids in the 
plant 


Plant No. 2. 
















Flowers 


26.67 

in- 55 


4-55 
16.63 


82 

85.O8 


2 . 04 
7-50 


.0126 


•277 


I .21 


Flowering tops 


.1280 


.770 


12-33 




Leaves* 
Small 


21 .00 


2-95 

27.23 
2.32 


86.00 


I 12 

12 . 20 
I .04 


.Ol8l 


.613 

•571 

.839 


1.72 

I4.96 
I.87 


Large : 

Without petioles . 
Petioles 


183 .00 
21 .65 


85-14 

89.30 


-I555 
.OI94 




ii/iiLire icirgt 
leaves 


214.65 


29.55 


86.10 


I3.24 


•1749 


•592 


16.85 




Total 


235-65 


32.50 


86 .08 


I4.64 


.1930 


•597 


18.57 




Stems: 

Small 


141.70 

1 20 90 
82.30 
93.00 


18.48 

O "2/1 

y -o4 
9-5o 
25.07 


86.93 

92.27 
88.45 
73.00 


8.28 


.1417 

•OI45 
.0326 


.767 

IT? 

•153 
.130 


I3-63 

1-345 
3-14 


Large : 

Pith 


4.18 


Bark 


4.17 

11-23 


Wood 




Entire large 
stems 


296 .20 


43 .91 


85.20 


19.67 


.08l8 


.186 


7.88 


Total 


437-90 


62.39 


85.80 


27-95 


■2235 


-358 


21.51 




Roots: 

Small 


105.50 

364-30 
266.70 


16.47 

53-71 
36.93 


84.40 

85.32 
86.07 


7-38 

24.07 
16.59 


•0974 

.2572 
.1274 


•592 

•479 
•345 


9-36 

24-75 
12 .27 


Large : 

Wood 


Bark 




Entire large 
















roots 


630.00 


90.64 


85-61 


40.61 


•3846 


-•424 


37.02 




Total 


735-50 


107 .11 


85-44 


52.52 


.4820 


•450 


46.38 


Entire plant 


1.538.27 


223 . 18 


85-49 




I .0391 


.466 











Am. Jour. Pliarm. > 
March, 1914. / 



Alkaloids in Belladonna Plant. 



IOI 



Table I. — Continued. 
Analyses of Four Typical Third-year Belladonna Plants. 



Plant and part 



Plant No. 3- 

Flowers 

Flowering tops. . 



Leaves : 

Small 

Large: 

Without petioles 
Petioles. . . 



Entire large 
leaves 



Total. 



Stems : 
Small. . . 
Large : 

Pith.. 

Bark. 

Wood 



Weight (grams) 



Green 



Dry 



Entire large 
stems 



Total. 



Roots : 

Small. . . 

Large : 
Wood 
Bark. 



29-75 
[04 .00 



5-26 
6.29 



28.00 4.57 

186.83 28.36 
18 .67 1 . 69 



205.50 30.05 



233-50 



34.62 



125.80 

119.30 
84.60 
98.50 



302.40 



428 .20 



212 .80 



449.90 
216 . 10 



17-49 

7.24 
7.98 
26.86 



42 .08 



59-57 



36.33 

70.54 
36.40 



Entire large! 

roots 666 . 00 I 106 . 94 



Total 878.80 



Entire plant 1,674.25 



143-27 



259.01 



Moist- 
ure 
per 

cent. 



82.30 
84.32 



83.70 

84.88 
90.99 



85.4O 



85.IO 



86.08 

93-49 
9035 • 
72.70 



Per^ 
cent, of 
entire 
plant 



2.03 
6 .29 



1 -77 

10.95 
•65 



11 .60 



13.29 



6-75 

2.80 
3.08 
10.37 



86. 13 j 16 .24 



86.10 22.99 



82.97 I 14.03 
84.30 27.23 



83.20 



83-93 



83.70 



84-53 



1405 



41.29 



55-31 



Alkaloids 



Grams 



OI9I 
1379 



Per 
cent. 



366 
•847 



.0305 .669 



.1273 
OO59 



449 
354 



1332 -443 



1637 .472 



.0222 
0113 
.0306 



.0641 



1533 



2365 

3900 
1114 



5014 



7379 



21 19 



.510 

•307 
.142 
.114 



152 



257 



.651 

•553 
• 306 



.469 



515 



,468 



Percentage 
of quantity 

of alka- 
loids in the 
plant 



102 



Alkaloids in Belladonna Plant. 



Am. Jour. Pharm. 
March. 1914. 



Table I. — Continued. 
Analyses of Four Typical Third-year Belladonna Plants. 





Weight (grams) 






Alkaloids 


Plant and part 


Green 


Dry 


Moist- 
ure 
per 

cent. 


Per 
cent, of 
entire 
plant 


Grams 


Per 
cent. 


Percentage 
of quantity 

of alka- 
loids in the 
plant 


Plant No. 4 
Flowers 


41 .60 
91 .OO 


8 .00 


80.60 


2.83 

5-79 


•0361 
. 1607 


•452 
.982 


3-oo 
I3-36 


Flowering tops 


I6.37 


82 .OO 




Leaves : 

Small 


28.60 


5 00 


8l .40 

83.60 
91.30 


1 77 

10.79 
•57 


•0378 

. 1026 
.OO81 


•757 

•337 
.502 


3-14 

8-53 
.68 


Large : 

Without petioles . 
Petioles 


I85.50 
18 .60 


30.48 
1 .62 




Entire large 
leaves 


204. 10 


32.10 


84.24 


1136 


.1107 


■345 


9.21 




Total 


23O.9O 


37.10 


83-75 


13-13 


•1485 


.400 


12-35 




Stems: 


195.60 

140.20 
118 .00 


22.50 

10.37 
12 .31 


88.50 

92 .60 
89.58 

73-30 


7.96 

3-67 
4 63 
13-55 


•1597 

•0431 
.OI36 
.0486 


.710 

.416 
.111 


13.28 

3-59 
1 13 
4 03 


Large : 

Pith 


Bark 


Wood 


138.30 


38.29 


. 127 




Entire large 
stems 


396.50 


60.97 


84. 6s 


21 s8 


•1053 


•173 


8-75 




Total 


592.10 


83-47 


85-95 


29-54 


.2650 


.318 


22 .03 




Roots: 

Small 


196.20 

41530 
229.30 


35 65 

63.62 
38.34 


81 .80 


12 .62 


•I750 

•3047 
.1127 


.491 

•479 
.294 


14-55 

25-33 
9-38 


Large : 

Wood 


84-75 
83" -30 


22.52 
13-57 


Bark 




Entire large 
roots 


644 . 60 


101 .96 


84.20 


36.08 


.4174 


•409 


34-71 




Total 


840.80 


137.61 


83.61 


48.70 


•5924 


•430 


49.26 




Entire plant 


1,796 .40 


282.55 


84.27 




I .2027 


•425 











A \a J rXi P 9i4 rm 'l Alkaloids in Belladonna Plant. 103 



Table II. 

Comparison of Percentage of Alkaloids in Different Parts of Plants. 



Alkaloids (per cent.) 



Part of plant 










Average 


Fraction 
of aver- 




Plant 


Plant 


Plant 


Plant 


age total 




No. 1 


No. 2 


No. 3 


No. 4 


of 4 
plants 


alkaloids 
in 














4 plcints 


Flowers 


0.445 


O.277 


O.366 


O.452 


0.385 


2 .03 


Flowering tops 


.862 


.770 


.847 


.982 


•865 


1533 


T 

.Leaves '. 
















.079 


.013 


. 009 


*7 C *7 

•757 


.079 


3 00 


Large : 
















•37° 


At t 
. 07 I 


•449 


•337 


•434 


IO . 90 


Petioles 


•381 


.839 


•354 


.502 


.769 


■93 


Entire large leaves 


•378 


•592 


•443 


•345 


•439 


11.94 


Total 


•432 


•597 


.472 


.400 


•475 


14-95 


otems: 














Qmo1 1 


.441 


.707 


.510 


.710 


. 007 


10 . 4° 


Large : 














•337 


•372 


•3°7 


.410 


•35° 


2 -97 


Bark 


.128 


•153 


.142 


.111 


•134 


1. 17 


Wood 


.105 


.130 


.114 


. 127 


.119 


3i3 


Entire large stems 


.156 


.186 


•152 


•173 


.167 


7.27 


Total 


•237 


•358 


•257 


.318 


.292 


17 .62 


Roots : 














Small 


.508 


•592 


.651 


.491 


.561 


12.63 


Large : 














Wood. 


•433 


•479 


•553 


■479 


.486 


26.86 


Bark 


.310 


•345 


.306 


.294 


•314 


10.58 


Entire large roots 


•383 


•424 


.469 


.409 


.421 


37-44 


Total 


•398 


•450 


•5i5 


•430 


•448 


50.07 


Entire plant 


.418 


.466 


.468 


•425 


•444 











ward detached and kept separate. The berries were allowed to dry 
slowly in the air until the seeds and husks could be separated. The 
young sprouts, which were found mainly along the lower portions 
of the large stems, were from 2 to 4 inches long and consisted of 
tender growth of stem and leaves. Since these were first-year plants 
all the stems were rather small and none were large enough to be 



104 Alkaloids in Belladonna Plant. (\ J S r, Jir 



Table III. 

Analyses of Six Typical First-year Belladonna Plants. 



Plant and part 



Weight (grams) 



Green 



Dry 



Moist- 
ure per 
cent. 



Per 
cent, of 
entire 
plant 



Alkaloids 



Grams 



Per 
cent. 



Percent- 
age of 
total 
quantity 
in the 
plant 



Plant No. i 

Leaves 

Small 

Large 



Young sprouts. 



Fruit 

Calyx . . . 
Berries. . 

Seeds. 

Husks 



Stems. . 
Small . 
Large . 



Roots 

Entire plant. 



Plant No. 2 



Leaves. . 
Small. 
Large . 



Young sprouts. 



Fruit 

Calyx . . , 
Berries . . 

Seeds. 

Husks 



Stems . . 
Small. 
Large . 



Roots 

Entire plant. 



134.00 
78.35 
55-65 

58.20 

350.40 
72.65 

277-75 



352.8o 
181.30 
171.50 

215.80 



27.56 

15-94 
11 .62 

8.50 

67-35 
9-95 
57-40 
44-59 
12.81 

76.68 
40.72 
35 -96 

47-17 



.20 



83.40 
4i -65 
41-75 

59 -5o 

245.70 
60.55 
185-15 



225 .26 



18.38 
9.09 
9.29 



361.15 
198 .00 

163.15 
167-90 
897-65 



54 

8 

45 
33 
12 

66 
35 
30 

J6 

182 



79 



12.23 
7.07 
5-i6 

3-77 

29.90 
4.42 
25-50 
19.86 
5.64 

34 05 
18.20 

15-93 
20.94 



70 



77 


9 


10 


■05 


78 


3 


4 


97 


77 


6 


5 


08 


83 


2 


3 


60 


78 


•5 


29 


78 


79 


.8 


4 


58 


75 


•3 


25 


20 






18 


55 






6 


65 


81 


3 


36 


50 


82 


1 


19 


60 


81 





16 


90 


78 


1 


20 


07 



79-7 



1463 
0906 

0557 

0680 

1816 
0084 
1732 
1536 
0196 

0752 
0493 
0259 

2040 
6751 



•ii37 
•0594 
•0543 

.0629 

. i960 
.0126 

.1834 
.1618 
.0216 

.0788 
.0566 
.0222 

•1793 
.6307 



53i 

569 
479 

799 

269 
085 
302 

344 
153 

098 
121 
072 

432 



21 .67 
13-42 
8.25 

10.07 

26.90 
1.24 
25-66 
22.75 
2 .91 

11 . 14 

7 -30 
3-84 

30.22 



299 



619 

654 
586 

953 

361 
152 
399 
479 
178 

118 
158 
072 

488 

346 



18 


•03 


9 


.42 


8 


.61 


9 


•98 


3i 


.08 


1 


•49 


29 


09 


25 


65 


3 


43 


12 


49 


8 


97 


3 


52 


28 


42 



Am. Jour. Pharm. 

March, 1914. 



Alkaloids in Belladonna Plant. 



105 



Table III. — Continued. 
Analyses of Six Typical First-year Belladonna Plants. 






Weight 


(grams) 










Alkaloids 


* 

Plant and part 










Mc 
ure 


)ist- 
per 


Per 
cent, of 
entire 






Percent- 
age of 




Green 


Dry 


cent. 


plant 


Grams 


Per 
cent. 


total 
quantity 
























in 


the 
























plant 


Plant No. 3 


























Leaves 


107 


57 


25 


•44 


76 


40 


II 


.28 


•1305 


514 


20 


.06 


Small 


70 


40 


16 


■56 


76 


40 


7 


•33 


.0907 


•548 


13 


•94 


Large 


37 


1 7 


Q 
O 


. CO 


76 


. 00 


3 


•95 


.0398 


•448 


6 


. 12 




46 


95 


8 


.04 


82 


90 


3 


56 


.0708 


■877 


10 


•87 


Fruit 


337 


40 


66 


83 


80 


IO 


29 


63 


.2014 


.302 


30 


93 




77 


4o 


1 


79 


86 


OO 


4 


71 


.0091 


.085 


I 


•39 


Rpi*np<; 


259 


95 


56 


. I I 


78 


30 


24 


90 


.1923 


•343 


29 


54 


Seeds 






A A 

44 








t n 
A 9 


6/1 
D 4 


•1733 


•391 


26 


61 
























Husks 






1 1 


.86 






5 


26 


.OI90 


. 160 


2 


92 




363 


50 


77 


03 


79 


OO 


34 


15 


.0564 


•073 


8 


66 


Small 


154 


10 


31 


93 


78 


OO 


14 


15 


. 0298 


•°93 


4 


58 


Large 


209 


40 


45 


. 10 


78 


50 


20 


OO 


.0266 


•059 


4 


08 




197 


15 


48 


23 


75 


5° 


21 


38 


. 1920 




29 


48 


Entire plant 


1,052 


57 


225 


57 


78 


60 






.6511 


.288 


















Plant No. 4 


























Leaves 


142 


30 


27 


59 


80. 


70 


10 


•45 


.2038 


•736 


20 


37 


•vmpll 


68 


65 


13 


13 


81 


00 


4 


95 


nr> t ft 
. 09 I 


. 090 


9 


17 




73 


65 


14 


46 


80 


40 


5 


50 


.II20 


•772 


11 


20 


Young sprouts 


5i 


92 


8 


21 


84 


20 


3 


12 


.O849 


I .032 


8 


49 


Fruit 


398 


80 


75 


34 


81 


05 


28 


56 


.2810 


•373 


28 


09 


Calyx 


109 


45 


13 


90 


87 


10 


5 


28 


.0294 


.211 


2 


94 


Berries 


289 


35 


61 


•44 


78 


80 


23 


28 


.2516 


.409 


25 


15 


Seeds 






49 


20 






18 


66 


.2170 


.441 


21 


69 














Husks 






12 


24 






4 


62 


.O346 


■283 


3 


46 
















Stems 


400 


05 


82 


63 


79 


20 


3i 


32 


.1156 


. 140 


1 1 


55 


Small 


183 


10 


36 


93 


78 


60 


14 


00 


.0661 


.179 


6 


60 


Large 


216 


95 


45 


70 


78 


90 


17 


32 


•0495 


.108 


4- 


95 


Roots 


238 


35 


70 


00 


70 


90 


26 


55 


•3I50 


•450 


31 


50 


Entire plant 


1,231 


77 


263 


77 


78 


30 




I .0003 


•379 















io6 



Alkaloids in Belladonna Plant. 



f Am. 

1 i 



Jour. Pliarm. 
March, 1914. 



Table III. — Continued. 
Analyses of Six Typical First-year Belladonna Plants. 



Plant and part 



Weight (grams) 



Green 



Dry 



Moist- 
ure per 



Per 
cent, of 
entire 
plant 



Alkaloids 



Grams 



Per 
cent. 



Percent- 
age of 
total 

quantity 
in the 
plant 



Plant No. S 



Leaves. . 
Small. 
Large. 



Young sprouts. 



Fruit 

Calyx . . . 
Berries . . 

Seeds. 

Husks 



Stems. . 
Small. 
Large. 



Roots 

Entire plant. 



Plant No. 6 



Leaves. . 
Small. 
Large . 



Young sprouts. 



Fruit 

Calyx . . . 
Berries . . 

Seeds . 

Husks 



Stems . . 

Small. 

Large . 
Roots . . 



Entire plant. 



113-75 
60.05 
53-7o 

51-95 

295.60 
75.06 
220.60 



331-75 
192.05 
139.70 



23-41 
12.51 
10.90 

7-52 

58.72 
9.69 
49 03 
37- 80 
11 .14 

62.13 
35 30 
26.83 



126.50 31.90 



919.55 183.68 I 81 



107.65 
57-40 
50.25 

37-55 

335-85 
80.15 
255-70 



380.70 
244.00 
136.70 
221 .50 



1,083.25 



80 



73 



50 



98 



20.72 80.70 
10.97 I 80.89 
9-75 j 80.59 

6.21 83.25 



61 .29 
9 -5o 
51-79 
37-28 

14-51 



81.50 
88.10 
79.70 



70.67 81 .40 
43.32 82.00 
27-35 79-90 
47-54 I 78.30 



12 .69 
6.80 
5-89 

4. 10 

31-99 
5-27 
26.72 
20.65 
6.07 

33-84 
19 .22 
14.62 

17-38 



206.43 80.94 



10.04 
5-3i 
4-73 

3.01 

29 .69 
4.60 
25.09 
18.06 
7-03 

34-23 
21 .00 

13 .23 
23-03 



.2135 
.1113 
. 1022 

.0790 

•1957 
.0148 
.1809 
•i55o 
.0259 

.0892 
.0626 
.0266 

.1674 



7448 



1662 
0873 
0789 

0545 

.1700 
.0132 
.1568 
•1 193 
•0375 

.0874 
.0724 
.0150 
.2247 



7028 



913 

890 

938 
052 

333 
221 

370 
409 

233 

144 
177 
099 

524 



405 



803 
794 



,876 

.277 
139 
■305 
.320 

259 

.114 
.167 
•055 
•472 



340 



Am. Jour. Pharm. 
March, 1914. 



Alkaloids in Belladonna Plant. 



107 



separated into bark, wood, and pith. The roots also were much 
smaller than in the older plants and were therefore not separated 
into large and small roots. 

In assaying the seeds it was necessary first to extract the fixed 
oil with petroleum ether. The percentage of alkaloids, however, as 
given in Table III, is calculated on the basis of the whole seeds. 

Table IV. 

Summary Showing Comparison of Percentages of Alkaloids in Different Parts 

of the Six Plants. 



Part of plant 



Alkaloids (per cent.) 



Plant 
No. 1 



Plant 
No. 2 



Plant 
No. 3 



Plant 
No. 4 



Plant 
No. 5 



Plant K lf^ Q 

No. 6 ° f a " 
1 plants 



Fraction 
of average 

total 
alkaloids 
in 6 plants 



Leaves 

Small 

Large 

Young sprouts 

Fruit 

Calyx 

Berries .... 
Seeds. . . . 
Husks . . . 

Stems 

Small 

Large 

Roots 

Entire plant. . 



o.53i 
569 
479 

799 

269 
085 
302 
344 
153 

098 
121 

072 

432 



0.619 

654 
586 



953 



299 



361 
152 
399 
479 
178 

118 
158 
072 



346 



0.514 
548 
448 



877 

302 
085 
343 
39i 
160 

o73 
093 
059 

397 



0.736 
698 
772 

032 

373 
211 
409 
441 

283 

140 
179 
108 

45o 



288 



0.913 
890 
938 

052 

333 
221 

370 
409 
233 

144 
177 

099 

524 



379 



405 



803 

794 
808 

876 

277 
139 
305 
320 

259 I 

114 
167 
055 

472 



340 .3430 



6860 
6922 
6718 

9315 

3192 
1488 
3572 
3973 
2110 

1 145 
1492 

0775 
4605 



22 . 10 
12.05 
10.05 

9-53 

27.84 
1 .99 

25-85 
22.25 
3.60 



11 .41 

7.65 
3-76 

29.11 



A critical review of Tables I to IV leads to the conclusion first 
of all that in a general way the distribution of alkaloids in the 
different parts of belladonna plants is largely the same in different 
individual plants. While it is probably unwise to draw definite 
conclusions from the limited number of plants here analyzed, the 
results are without doubt largely indicative of what would be found 
were analyses made of many more plants. Gerard 2 has found that 
in both wild and cultivated belladonna plants the leaves, roots, fruit, 

2 Gerard, A. W. Report on the alkaloidal value of cultivated and wild 
belladonna plants, Yearbook of Pharmacy, 1880-1881, pp. 482-489. 



io8 



Alkaloids in Belladonna Plant. 



(Am. Jour. Pharm. 
\ March, 1914. 



and stems rank in the order named as regards the percentage of 
alkaloidal content. These observations are in perfect accord with 
the results here given. A number of interesting facts are emphati- 
cally brought out. Of the aerial part of the plant all parts but the 
large woody stems contain enough alkaloids to make their utilization 
practicable. During the early summer, belladonna herb, including 
leaves, tops, and small stems, could be advantageously picked as far 
as medicinal strength is concerned if the herb rather than leaves 
were official. The flowering tops in the third-year plants easily 
rank first as containing the greatest percentage of alkaloids. In all 
the first-year plants, the young sprouts are found to contain the 
greatest quantity of alkaloids, two of the six containing more than 
i per cent. Attention has been directed to the fact that the flowering 
tops and the young sprouts represent the youngest and tenderest 
growth in the third-year and in the first-year plants, respectively. 
Since in the plants analyzed the greatest concentration of alkaloids 
is found in these parts, the logical conclusion is that the greatest 
concentration of alkaloids is to be found in the youngest parts of the 
plants. A further study of the tables will emphasize this fact still 
more. In seven of the ten plants the small leaves are considerably 
richer in alkaloids than the large leaves, the average for the small 
leaves being 0.687 per cent, and for the large ones 0.578 per cent. 
The small leaves usually appear on the plants later than the large 
ones. In the case of the third-year plants, which were analyzed in 
June, the small leaves were found mostly near the tops of the 
branches, indicating that they represented younger growth than 
the large leaves. Later in the season there is always a preponder- 
ance of small leaves, very little growth of large leaves taking place 
after the flowering period is over. Hence, in all the plants under 
consideration, the small leaves constitute in a general way younger 
growth than the large ones. The higher percentage of alkaloids in 
the former is, therefore, parallel to the condition that exists in the 
flowering tops and young shoots. Again it is seen that the same 
is true of the stems. The average per cent, of alkaloids in the small 
stems is 0.332, and in the large stems 0.113. The difference is 
especially marked in the third-year plants. Here again those stems 
which constitute the youngest growth are richest in alkaloids. In 
the four plants where the large and small roots were separated, the 
average alkaloidal content of the small roots was 0.561 per cent., and 
of the large roots 0.421 per cent. The small roots, as has been 



Am. Jour. Pharm. 

March, 1914. 



Alkaloids in Belladonna Plant. 



109 



stated, consisted mostly of the young and tender ends of the tap 
roots. The relationship is again evident. In the four third-year 
plants whose large stems and roots were separated into their various 



Fig. 



P£f? CEMT OF /4l O/DS 



PER CEA/r Of /tl/f/tl0/0S 

^^^^^^^^^ 
^ ^ § ^ ^ ^ ^ ^ 



<ZDC*n/ /T< v 



Graphic illustration showing the distribution of the alkaloids in the various parts of the 

Belladonna plant. 

parts, the average per cent, of alkaloids is as follows : Pith of stems, 
.0358; bark of stems, 0.134; wood of stems, 0.119; bark of roots, 
0.314; wood of roots, 0.486. Figure I shows graphically the dis- 
tribution of alkaloids in the plant. 




no 



Alkaloids in Belladonna Plant. 



Am. Jour. Pharm. 
March, 1914. 



It has been quite generally held that most of the alkaloids in the 
roots are found in the bark. The National Dispensatory states that 
a good root contains alkaloids in the parenchymal tissue of all parts 
though mostly in the bark, while in a woody root it is almost ex- 
clusively in the bark. This investigation appears to indicate that 
such is not always the case. In all of the four three-year old plants 
analyzed, the woody part of the roots was richer in alkaloids than 
the bark. In order to obtain further data on this question, seven 
four-year old plants were dug up early in the fall and the roots 
separated into bark and wood. Table V shows the results of the 
assays. 

Table V. 

Comparison of Alkaloidal Content of the Bark and Wood of the Roots oj 
Individual Belladonna Plant. 



Number of plant 



Alkaloids (per cent.) 



Bark 



O.I82 
O.163 
0.262 
O.I44 
O.205 
O.238 
O.227 



Wood 



0.217 
O.177 
O.324 
O.29O 

0.347 
O.447 
O.400 



These results show further that the bark is not always richer in 
alkaloids than the woody tissue. 

It has been pointed out that the small leaves were found to be 
almost invariably richer than the large leaves. This is a matter of 
some importance in that it becomes a factor in the method of pick- 
ing leaves with regard to securing those of greatest medicinal value. 
To establish this fact more conclusively, large and small leaves were 
picked from the individual belladonna plants. At the same time 
leaves were also picked from a number of species of Datura. Table 
VI shows the relative percentage of alkaloids in the leaves. 

It will be noticed that in only one instance, plant No. 2, 
does the sample of large leaves show a greater percentage of alkaloids 
than the smaller. In all the others the difference is greatly in favor 
of the small leaves, as is also indicated by the averages. All but one 
of the Datura species indicated the same condition, thus showing 



A \S; i P 9u. rm ' } Alkaloids in Belladonna Plant. in 

that the relative concentration of alkaloids in large and small leaves, 
as found in belladonna, exists also in other members of the solan- 
aceous family. Since the small leaves are as a rule younger than the 
large ones, it would seem that the greater concentration of alkaloids 
in the former is due to greater cell activity. It would be expected 
that there would be a general graduation in the concentration of 
alkaloids from the youngest to the oldest leaves. To determine this 
point two rows each containing about 75 plants were selected. From 

Table VI. 



Comparison of Alkaloidal Content of Large and Small Leaves from Individual 
Plants of Atropa Belladonna and Various Species of Datura. 





Alkaloidal 




Alkaloidal 




content of leaves 




content of leaves 


Plant analyzed 


(per cent.) 


Plant analyzed 


(per cent.) 




Large 


Small 




Large 


Small 


Atropa bella- 








0.268 


O.418 


donna : 






D. fastuosa No. 29646 


.438 


.478 


Plant No. 1 


O.342 


O.657 


D. gigantea 


.165 


.179 


Plant No. 2 


•743 


.706 


D. quercifolia 


.228 


.368 


Plant No. 3 


.685 


.915 


D. fastuosa No. 29644 


•423 


•479 


Plant No. 4 


.840 


.929 


D. stramonium inermis .... 


.221 


•511 


Plant No. 5 


.864 


.904 


D. tatula 


.218 


.241 


Plant No. 6 


.718 


.831 




.277 


.271 


Plant No. 7 


•537 


•723 


D. leichardti 


•175 


.189 


Plant No. 8 


.960 


I .074 




.190 


•454 


Plant No. 9 


•775 


.924 


D. stramonium (red stem) 


.176 


.381 


Plant No. 10 


•570 


.990 




•133 


•475 










.306 


.441 


Average . . . 


•703 


.865 




.247 


.378 



each row 8 samples of leaves were picked, ranging from the smallest 
to the largest. Each sample was taken from the entire row so that 
leaves from all the plants were included. By this means, the factor 
of individual plant variation was eliminated as much as possible. 
The following table shows the per cent, of alkaloids in each sample. 

In row No. 1 the average of the first and last four samples are 
0.639 anQl 0.308 per cent., respectively, while in row No. 2 the aver- 
ages are 0.695 an d 0402, respectively. It is evident that if too many 
of the larger leaves are included the sample will assay relatively low 
and will hardly give a fair indication of the value of the plant. There 
is a natural tendency to pick such leaves because they can be more 



112 Toxic Constituent of Poison Ivy. -j Al 

Table VII. 



Comparison of Alkaloidal Content of Belladonna Leaves, Varying in Size from 
the Smallest to the Largest, each Sample being a Collective 
Picking from the Entire Row. 



Row No. i. 


Row No. 2. 


Sample 


Alkaloids (per 
cent.) 


Sample 


Alkaloids (per 
cent.) 


i (smallest) 

2 

3 
4 
5 

6 

7 

8 (largest) 


0.62I 
O.706 
O.664 
O.766 
O.598 
O.406 
O . I IO 
O. Il6 


I (smallest) 

2 

3 

4 

5 

6 

7 

8 (largest) 


0.598 
O.700 
O.669 

.804 

O.605 
0.523 
0.324 
0.212 



rapidly picked owing to their size. It is economically out of the 
question to pick such leaves as constitute samples 1 and 2, while 
samples 3 to 6 should represent the best leaves available for all pur- 
poses, appearance as well as strength, and from both the medicinal 
and commercial standpoint. 



THE VOLATILE NATURE OF THE TOXIC 
CONSTITUENT OF POISON IVY. 

By Charles E. Bessey. 

There is a pretty general agreement among medical men that 
the active poisonous principle in Poison Ivy (Rhus radicans L., 
Toxicodendron radicans (L.) Kuntze) is a non- volatile oil, and 
that as a consequence poisoning without contact is impossible. Yet 
there are many assertions to the contrary by those who have been 
victims of this poisonous principle. I have heard persons assert 
that they had been poisoned when walking or driving by the Poison 
Ivy. I have always maintained a feeling of considerable doubt in 
regard to such cases, for it is obviously difficult to prove lack of 
contact. 

However, I myself once suffered from a severe case of poisoning 
without contact, as I reported a few years. ago in a paper entitled 
"A Preliminary Account of the Plants of Nebraska which are 



Am Ma J r°ch r ' Si*™ 1 ' } Toxic Constituent of Poison Ivy. 113 

Reputed to be Poisonous, or are Suspected of Being So," and pub- 
lished in the Annual Report of the Nebraska State Board of Agri- 
culture for 1901. This account is so detailed that I repeat it here, 
as follows : 

" An assistant brought into my laboratory a tin box full of 
plants, among which were many flowering specimens of the Poison 
Ivy. The day was hot, and the assistant had walked in the sun for 
a mile or more, in bringing in the plants. Knowing my suscepti- 
bility to Poison Ivy poisoning he warned me not to touch the tin 
box or its contents. I therefore told him to open the box while 
I looked on and selected the plants which 1 wished him to preserve 
for pressing. As the box was opened I leaned over and looked in, 
being very careful not to come into contact with the box or the 
plants. As the assistant took up plant after plant I pointed to 
others and asked him in regard to the stations where he secured 
them. I was very careful, as I had been very severely poisoned 
many times before, and did not wish to have another experience of 
the discomfort. Yet in a day or two I found myself suffering with 
the usual inflammation, only the surfaces affected were those only 
which had been directly exposed when I leaned over the box of 
plants. My face was inflamed all over, except where my beard, 
mustache, eyebrows, and nose made projecting protections. Above 
these there were small areas entirely free from inflammation. The 
under side of my eyebrows (the 'overhang') was thoroughly 
poisoned, and so was the inside of my nose (the nostrils). My 
right hand was severly poisoned, but here again the distribution of 
the inflammation was peculiar, being confined to the parts which 
were directed dozvnward as I pointed at the various specimens in 
the box. Thus the proximal and middle joints of the second, third 
and fourth fingers, and the under side of the wrist of that hand 
were badly affected, while the upper side of the hand was not 
poisoned at all. My left hand was not poisoned, and I account for 
this by the fact that it was kept back and not used in indicating 
plants to be examined by the assistant." 

I do not see how any one can escape from the conclusion that 
that which poisoned me so severely and so peculiarly was volatile 
enough to be carried up (apparently in straight lines) in the warm 
air which escaped from the tin collecting box (vasculum) when 
opened in my study. In this case there was no contact on my part 
with the Poison Ivy, nor with any other plants in the vasculum. I 



ii4 



had been poisoned too often to be careless when warned by my 
assistant. I am not denying the truth of Dr. Pfaff's conclusion that 
there is a non-volatile poisonous oil in the Poison Ivy. I am forced 
to conclude that there is a volatile poison, also, in this plant. 

The University of Nebraska. 



APPLIED PHARMACOGNOSY. 
Some Observations of a Graduate. 
By J. R. Rippetoe. 

What are you going to do one year from to-day or what will 
you be doing? You don't know, certainly not. If it were possible 
for you to know, wouldn't you prepare to make that day's work a 
success ? 

Did it ever occur to you to try and imagine what kind of a 
world this would be if every man could begin at his deathbed and 
live life back to birth or in other words live his life over again with 
the advantages of the experience and knowledge gained in his 
lifetime? Old age says my days have passed but youth is full of 
ambition and hopes for the future. 

The laws of nature give man only one life but the law of evolu- 
tion gives youth all the advantages of the experience of old age. 
We, therefore, in our lifetime take from the present and the past 
varying portions of its offerings. 

You are now learning the principles of Pharmacy and soon you 
will be as fully equipped as the learned professors and instructors 
in this college can teach you and as much as you are willing to learn. 

The point I want to take up with you is the application of your 
knowledge. Some of you will, no doubt, take up manufacturing 
pharmacy. Those of you who will take up retail pharmacy will 
find my remarks equally applicable to your position. 

What are the duties of a pharmacist or a pharmaceutical chemist 
in a pharmaceutical laboratory? 

The first operation is the writing of a working formula. If an 
official preparation is to be made this is not difficult, but I have 
seen some men spend several hours in trying to calculate the quan- 
tities of each ingredient when the formula may be given to them for 
one fluidounce or one tablet, as the case may be, and even then 



%ar°ch r ;i P 9ir m "} Applied Pharmacognosy. 115 

not have it correct. A formula may state the grains or minims in 
each fluidounce and for practical purposes it must be calculated to 
the proper quantities to make 100 liters. 

As many liquids are bought and sold by weight and it is also 
more practical to handle them by weight the minims must be con- 
verted into grammes and kilos. The specific gravity of the liquids, 
therefore must also be considered. Calculating many liquids to 
weight is absolutely necessary for figuring costs. 

The quantity to be made is primarily governed by the demand 
but there is to be considered among other things cost of raw 
material. This is particularly to be considered with crude drugs 
which at times offer about as much opportunity for speculation as 
stocks in Wall Street. With such drugs as ergot, jalap, ipecac, 
hydrastis and opium varying in price from 50 cents to $10.00 per 
pound and the price fluctuating with the season or crop it is neces- 
sary to keep an eye on the market and your stock and sales. 

The buying of crude material and selling of the finished products 
are of course taken care of by separate departments, but the manu- 
facturing comes in between and requires some knowledge of the 
buying and selling. The buying and selling departments offer 
good inducements to college trained men, the selling in particular 
to men who are more inclined to the commercial side rather than 
the scientific side of pharmacy. 

If a fluidextract or some drug preparation is to be made and 
there is no stock of crude drug on hand the purchase of drug is 
taken up with the buying department. The buying department asks 
for quotations and samples of the drug offered, especially if the 
drug is one that has some official standard. The samples are care- 
fully examined for freedom from foreign drugs and assayed for 
alkaloidal or extractive content. 

The analytical reports are compared and the price also taken 
into consideration for selecting the lot of drug to be purchased. 
With assayed drugs for example the price may not vary very much 
but the alkaloidal content may vary as much as 100 per cent. 

Since most drug preparations are made by extracting the drug 
with an alcoholic menstruum varying in strength from 10 to 95 
per cent, absolute alcohol, and alcohol costs about $2.50 per gallon 
by the barrel, means must be employed for carrying out the opera- 
tions to prevent loss in handling, evaporation and final recovery 
from the exhausted drug. 



n6 



Applied Pharmacognosy. 



/ Am. Jour. Pharm. 
\ March, 1914. 



All liquids are best handled by allowing them to flow from one 
vessel to another by gravity or by means of pumps to produce both 
pressure and vacuum as may be required. 

Ofttimes it is necessary to carry out a number of experiments 
to determine the best combination of alcohol and water, and some- 
times with glycerin or acid added, to extract the desirable con- 
stituents. 

In the making of pills and tablets, excipients or the proper liquid 
for granulating the ingredients are to be considered. This requires 
a knowledge of the properties of the ingredients. In making tablets 
the ingredients may be granulated by adding water, alcohol, ether, 
chloroform, petroleum benzin, other volatile liquids or combina- 
tions of these. 

Many formulas that are official in the U. S. P. or N. F. are 
practical for small quantities or immediate use but for large quan- 
tities and indefinite future use are not always satisfactory. The 
U. S. P. permits modification of the methods providing the finished 
products do not differ in their properties. Therefore, even in the 
official preparations, we have numerous problems for investigation. 
Elixir Iron, Quinine and Strychnine Phosphates U. S. P. is a 
splendid example of the manufacturers' problems and for that matter 
the retail druggist also. Every issue of the various drug Journals 
brings forth some new suggestion until it seems every one must have 
a different method for making it. 

Elixirs or similar preparations are very popular as a means for 
administering most any drug and I might say whether it has merits 
or not. They are often very troublesome to make. Prior to the 
Food and Drugs Act and even now, in some few cases everything 
seemed to be sacrificed for elegance in appearance, color, flavor, etc., 
and the ingredients claimed to be present were conspicuous by their 
abscence excepting in the very imposing gun-shot formula upon the 
label. 

The pharmacist in filling a prescription can excuse his or the 
physician's unintended precipitating mixtures by putting on a 
" shake well " label but not so with the pharmaceutical manufacturer. 
Only clear non-precipitating preparations can be sent out, and there 
must not be any changing in color and ofttimes druggists expect 
them to stand storage in zero temperature and serve for a window 
display in a window subject to the sun's rays throughout the day. 

We must, therefore, consider the solubility, stability, incom- 



Am. Jour. Pharm. ) 
March, 1914. / 



Applied Pharmacognosy. 



117 



patibility or means for controlling any one or all of these properties 
of each and every ingredient in the preparation. And last but not 
least the color and flavor must be pleasing to the eye and taste. 

It is these characteristics, the last two in particular, that have 
built up the pharmaceutical manufacturer's business at the expense 
of the druggist, and the physician's ability as a prescription writer. 

You might think the manufacturer has his formulas all highly 
perfected and there is nothing more to be done. This is not always 
the case. Purer chemicals are produced, solubilities and incom- 
patibilities may be changed or some new procedure of manipulation 
is learned. We therefore have before us a continual line of sub- 
stances and preparations for research. 

If a new or modified formula is to be made up it is always ad- 
visable to make up a small quantity, taking note of each step and 
carefully observing just what reactions take place. Possibly a 
number of combinations are indicated and about the only way to 
prove their value is to make up the combinations and test them 
out under all conditions. Each lot may be divided into portions 
and one of each placed in the sunlight, a hot closet, an ice box, 
humid atmosphere and a control under normal conditions. 

When the satisfactory combination is decided upon, the manipu- 
lation and apparatus for handling large quantities is to be con- 
sidered. 

Means for weighing and measuring, mixing, mechanical appa- 
ratus, kettles for heating, filtering, storage, bottling or filling pack- 
ages are problems always to be solved. Since the difference between 
raw material and finished product is labor, practical apparatus and 
economical manipulation stand between profit and loss. 

After the preparation is finished and ofttimes during the opera- 
tion various assays are made to check up the process, also for 
standardized preparations which are usually made overstrength 
and adjusted by assay. Fluidextracts, elixirs, syrups, etc., are 
assayed for alcohol, alkaloids, extractive, specific gravity ; tablets 
and pills for weight and ingredients ; ointments for grittiness, also 
powders ; emulsions for efficiency of emulsification, etc. 

As the majority of men seeking employment in a pharmaceutical 
laboratory prefer to get into the analytical department I want to 
say a few words about the work. I don't mean to be sarcastic or 
to ridicule any one, but I want to point out to you the problems by 
telling you how they should not be done. 



ii8 Applied Pharmacognosy. [ 

I trust that every student in this audience will receive his diploma 
at the appointed time. We occasionally meet students who go to 
college for a diploma and not an education. I recall a classmate 
of mine who took his freshmen year in this college and did not show 
up again until the senior year. He stated that he had spent his 
junior year in another college taking a Ph.G. degree and by re- 
turning here for the senior year would receive another degree. Pos- 
sibly, a man with as much ability to corner the market in degrees 
will succeed in his own way. 

Many graduates seem to think that with commencement study 
ends. If that is the way you feel about it you want to change your 
future plans at once. 

I recall a former analytical assistant of mine who considered 
attending pharmaceutical and chemical association meetings and 
the reading of journals a waste of time. His work was typical of 
his knowledge. 

Upon asking him why he ignited a tablet, which had been given 
him to test for morphine, he replied that he was going to test the 
ash for the morphine. When told he was not getting the results 
he should in making a preparation he stated that he had not studied 
it in college. If I felt that way about my work I would have to stay 
in college the balance of my life. 

One of the most essential things in your work is several good 
drug journals and if interested in chemistry a journal on chemistry 
also. They are absolutely necessary if you want to keep abreast of 
the times. You may have plenty of ideas of your own to keep you 
busy but the other fellows have some too and unless you take ad- 
vantage of the new discoveries that are being announced every day 
it won't be many years until you will find yourself surrounded by 
cobwebs of a vintage of the year you graduated. 

Some men will say I haven't the time to" read journals or I 
haven't the money. Membership in the American Pharmaceutical 
Association is $5.00 a year and the best drug Journal can be had for 
$r.5o per year. Two cents a day will pay for them. As to time, 
thirty minutes a day would more than suffice to read every line in 
the two publications and at the same time do a little thinking, also 
to see that each number is put away in some systematic manner for 
future reference. 

I recall two men who have been my assistants by the way they 
did analytical work with pencil and paper rather than with the bal- 



1914™'} Applied Pharmacognosy. 119 

ance and burette. Why all this detail anyhow ? The U. S 1 . P. contains 
many tests and assays for determining the purity of the official 
preparations, but these men seemed to think that since the majority 
of samples received for testing were all right, they could make a 
guess at the purity, figure the results backward and get out of doing 
the tedious work which for them required too much patience. Quite 
naturally their methods were soon detected and fortunately no harm 
came of it outside of the laboratory. But we cannot say as much for 
them. They were destroying their self-respect, ambition and their 
opportunities for success. 

These are the kind of men you are most likely to hear saying 
in after years, " I never had a chance." 

Confidence in your ability is essential but some men are so con- 
ceited about it that they become blinded to their errors. It might 
be all right to have the other man believe you thoroughly capable 
but you should not let that feeling prejudice the analysis of your 
own mind and knowledge. When the other man finds you out his 
confidence in you will be very much weakened. 

This failing may be attributed to several reasons. It is usually 
due to narrow-mindedness, snobbishness, false pride, all of which are 
due to ignorance. It indicates the failure to have grasped the 
primary objects in attending college, namely, to obtain a knowledge 
of the basic principles of the subject and the failure to continue the 
line of study after leaving college. Give the text-books you are 
using here the most prominent place in your future undertakings 
and add to them from time to time when some good book useful, 
particularly for reference, is called to your attention. These books 
with the Journals mentioned before are the backbone of your 
success. Speaking of mistakes, I recall a former assistant who was 
very confident of his ability and would have you believe that his 
knowledge was complete, he could make any kind of an analysis, he 
could not be in error. He said he was not in error when he obtained 
a result much too low in assaying a sample of ipecac but the method 
was faulty. He tried it again several times, always obtaining a 
different result which was much too low. After his last failure I 
picked up a beaker which he had used for evaporating the etherial 
solution of the alkaloids and subsequent titration and called his 
attention to the resinous mass of alkaloids coating the side of the 
beaker which he had failed to dissolve in the volumetric acid solu- 
tion. Another man required over one day to find out that a sample 



120 



The Assay of Zinc Stearate. 



{Am. Jour. Pharm. 
March, 1914. 



labelled sodium thiosulphate was not what it was labelled, and then 
he spent several hours more in finding out that it was potassium 
nitrate. 

I could tell you of many more such incidents. It is almost 
unbelievable that men who have been graduated by leading institu- 
tions of learning can be so helpless. The problems of the com- 
petition of life bring us to our senses and then we realize the op- 
portunities that have been thrown away. 

Coming back to my opening question, " What are you going to 
do one year from to-day?" If you take advantage of the oppor- 
tunities before you during the year, you will be well equipped to 
consider with intelligence any problem that may be presented to you 
one year from to-day. 



THE ASSAY OF ZINC STEARATE. 
By Hans Gesell. 

In the last few years the use of Zinc Stearate as an antiseptic ■ 
and astringent has been constantly increasing; it is rather difficult, 
however, to obtain this salt free from impurities, namely alkalies, 
alkali earths, chlorides, and oleates. The tests in the Pharmacopoeia 
do not give concordant results, so there is no question of the de- 
sirability of assay methods which will be accurate, yet simply and 
rapidly carried out by analysts. An excess of Zinc Oxide and Zinc 
Oleate seem to be the most frequent admixtures. 

The usual analytic method by which the stearic acid is liberated 
by means of hydrochloric acid and floats on the surface of the hot 
liquid, also holds good for any Zinc Oleate present, and if not in 
excess, will even congeal with the stearic acid on cooling. This 
difficulty can easily be overcome as follows : 

Take I gm. of Zinc Stearate and heat with 10 c.c. of distilled 
water and i c.c. of hydrochloric acid. The Stearic and oleic acid 
will be liberated and float as an oily layer. Let cool and this layer 
will solidify. Pour off acid liquid and wash the cake several times 
with water. Let dry. Determine the melting point. Pure Sfearic 
acid melts at 69 , but as the Stearic acid of the market usually con- 
tains Palmitic acid, the melting point is usually 55— 56 . Therefore, 
the melting point of this cake should not be below 55 — a lower 
melting point would surely point to the presence of oleic acid. 



Am. Jour. Pharm. ) 
March, 1914. J 



Sale of Bichloride Tablets. 



121 



The residue after incineration which is chiefly Zinc Oxide should 
be about 13 per cent. It is certain Zinc Oxide does not harm in a 
preparation of this nature, yet it is advisable to determine if it is 
really Zinc Oxide. It is best done in the following manner : 

Take 5 gm. of Zinc Stearate, add 10 c.c. of V2 N HC1 and warm 
gently until all the Zinc Stearate is decomposed. Then with y 2 N 
NaOH (Dimethyl Orange) titrate back the hydrochloric acid not 
used. Subtract this from the 10 c.c. taken, multiply it by the factor 
of Zinc Oxide, divide by the weight of Zinc Stearate taken, this will 
give the amount of Zinc Oxide in the compound. The Stearic acid 
could also be liberated and determined here, by simply separating 
the two liquids (warm), rejecting the aqueous portion, using phenol- 
phthalein as indicator and titrating with y 2 N NaOH. 

In a series of 5 experiments the following results were obtained : 



Melting point 


Residue after incineration 


Zinc found 


49—50° 
55-56° 
55—56° 

54— 55° 

55- 56° 


19.3 per cent. 
13.6 per cent. 
13 .8 per cent. 
14 .6 per cent. 
18 .7 per cent. 


15 . 1 per cent. 

10 .8 per cent. 

10.9 per cent. 
1 1 . 2 per cent. 
14.8 per cent. 



THE SALE OF BICHLORIDE TABLETS. 1 

♦ A Discussion of the Need for Restriction of the Sale and 
Distribution of Bichloride of Mercury Tablets. 

By Martin I. Wilbert, 

Technical Assistant, Hygienic Laboratory, United States Public Health Service. 

Some months since an alleged case of accidental poisoning by 
corrosive mercuric chloride, in Macon, Ga., was " featured " in 
practically all of the daily papers of the United States in such a way 
as to lead the unknowing to infer that poisoning by this substance 
guaranteed not alone a sure but also a painless death. 

The notoriety given this case was followed by an apparently un- 
usual number of corrosive sublimate fatalities, reported from the 

1 Reprint from the Public Health Reports, vol. xxviii, No. 46, Nov. 14, 
1913. 



122 



Sale of Bichloride Tablets. 



( Am. Jour. Pharm. 
\ March, 1914. 



various parts of the United States; and the publicity given to the 
harrowing details in connection with several of the cases was in 
turn followed by agitation for legislation on the part of some of 
the firm believers in the power of statute law to right all wrongs 
and to correct or, better, to prevent all possible abuses. 

Bills designed to restrict fatalities from the accidental taking of 
tablets containing corrosive mercuric chloride have been introduced 
in several of the State legislatures. In Pennsylvania, an act pro- 
hibiting the sale of bichloride of mercury at retail except upon the 
prescription of a registered physician was adopted by both houses of 
the legislature, but vetoed by the governor for the reason that " the 
public is amply protected regarding this drug by the restrictions put 
upon the sale of other poisons. Besides, I am informed that it is a 
household commodity." As the agitation for special legislation to 
restrict or at least regulate the sale of tablets of corrosive mercuric 
chloride is destined to be revived by the supposedly accidental poi- 
soning of a Brooklyn business man and to continue for some time to 
come, it may be of advantage to review briefly the several factors 
involved, the abuses really existing, the propositions that have been 
made to correct them, the safeguards already established, and the 
possible ways and means of bringing about desirable changes. 

While it will generally be admitted to be impracticable to prevent 
suicide or violent death by law or regulation, it is nevertheless well 
recognized that despondent and melancholy humanity is ever ready 
to seize upon any suggestions that offer sure, speedy, and painless 
death, so that every report of death, accompanied by the details of 
the means and methods producing it can be counted on as an incen- 
tive for other deaths brought about in much the same way. 

It is perhaps unfortunate that, for the rational study of the prob- 
lem before us, no definite and satisfactory information is available 
as to the conditions actually existing in our own country. Our 
mortality statistics give only general death rates and standardized 
death rates, without furnishing any, even approximate, information 
regarding the nature of the poison used or taken in cases of reported 
fatalities. There is, however, available in the report of the registrar- 
general of births, deaths, and marriages for England and Wales, 
a detailed account of the nature and kind of substances used, both 
in suicides and in accidental deaths, and a careful study of the tables 
herewith presented will suffice to demonstrate the impracticability 
of legislating specifically for any one poison. The tables also at 



Am. Jour. Pharm. ) 
March, 1914. j 



Sale of Bichloride Tablets. 



123 



least suggest the fact that there is probably little or no cause for 
undue excitement in regard to the possible number of deaths from 
the internal use of corrosive mercuric chloride and that, granting 
that conditions in England and this country are much the same, 
corrosive mercuric chloride plays but a minor part in the number of 
deaths due to ingested poison. This fact is further emphasized when 
we realize the very widespread use and, incidentally at least, abuse, 
of tablets of corrosive mercuric chloride and the comparatively few 
fatalities on record resulting from its internal administration. Even 
a careful search of the literature since the report of the case at 
Macon, Ga., shows that possibly 15, certainly not over 20, deaths 
have been reported from the ingestion of corrosive mercuric chloride 
since that time. When we remember that in the registration area 



Suicides and accidental deaths from scheduled poisons reported by the 
registrar-general of births, deaths, and marriages for England 
and Wales for the year 1911. 



Poison. 


Suicides. 


Accidental deaths. 


Total 
deaths. 


Male. 


Fe- 
male. 


Total. 


Male. 


Fe- 
male. 


Total. 


Aconite and belladonna liniment 






I 




I 




2 


Antimony (?) 








I 




I 


I 


Arsenic 


4 




5 


I 


2 


3 


8 


Atropine 


2 




2 








2 


Belladonna 






1 


I 


3 


4 


5 


Belladonna liniment 


1 




1 








1 


Cantharides 










I 






Carbolic acid 


32 


57 


'89 


6 


4 


10 


99 




1 




1 


2 




2 


3 


Chlorodyne 


1 


I 


2 


1 


3 


4 


6 


Chloroform 


1 




1 




1 


1 


2 


Cocaine and aconite 


1 




1 








1 


Cresolene 




2 


2 








2 


Hydrocyanic acid 


22 


2 


24 


3 




3 


27 


Lysol 




2 


3 ^ 








3 


Mercuric chloride; 


3 


2 


5 


2 




2 


7 


Narcotic (kind not stated) .... 


1 




1 


4 


2 


6 


7 




7 


I 


8 








8 


Opium (laudanum and morphine) 


37 


II 


48 


41 


17 


'58 


106 




42 


33 


75 


5 


10 


15 


90 


Paregoric 










1 




1 


Potassium cyanide 


33 


3 


36 


5 




5 


41 


Strychnine 


7 


6 


13 


1 


3 


4 


17 


Sulphonal 








2 




2 


2 




1 




2 








2 




1 




1 




1 


1 


2 






1 


1 








I 


Total 


198 


125 


323 


75 


49 


124 


447 



124 



Sale of Bichloride Tablets. 



Am. Jour. Pharm. 
March, 1914. 



Suicides and accidental deaths from non-scheduled substances reported by the 
registrar-general of births, deaths, and marriages for England 
and Wales for the year iqii. 



Poison. 



Acetanilide 

Acetic acid 

Alcohol 

Ammonia 

Camphor 

Camphorated oil 

Caustic potash 

Caustic soda 

Chloride of lime 

Chromic acid 

Disinfectant (?) 

Hartshorn and oil 

Hydrochloric acid 

Liniment (?) 

Mercury (?) 

Methylated spirit 

Nitric acid 

Paraffin 

Pennyroyal 

Phosphorus 

Potassium bichromate. . . 
Potassium binoxalate . . . . 

Potassium bromide '. 

Potassium permanganate. 

Saltpeter 

Sulphate of copper 

Sulphuric acid 

Veronal 

Whisky . . . 

Zinc chloride 

Kind not stated 



39 



Total 99 



Suicides. 



Male. 



43 



Fe- 
male. 



Total. 



Accidental deaths. 



Male. 



30 

2 



73 

2 



6o 



2 
I 

19 



83 



82 



68 



Fe- 
male. 



Total. 



47 



2 
I 

26 
I 
I 

2 

I 
I 

2 

I 
I 

2 
2 

3 
17 

i 

28 
ii5 



Total 
deaths. 



I 

2 
2 
22 
2 
2 



I 

3 
i 

99 
3 

2 
2 

4 

2 
10 

4 
4 
i 

3 

2 



19 
i 
i 

88 
297 



of the United States upward of 5000 deaths from acute poisoning 
are reported annually, even these apparently large figures are sug- 
gestive as being comparable with those included in the appended 
tables copied from the report of the registrar-general for England 
and Wales. 

Corrosive mercuric chloride was introduced as an antiseptic in 
surgical procedure more than 30 years ago, and for two decades at 
least was widely known by the popular names " corrosive sublimate," 
" bichloride," or " sublimate," and used in the form of solutions for 
a variety of purposes. This widespread use led to its employment 



Am Ma J rXm4. rm 'j Sale °f Bichloride Tablets. 125 

in other directions, so that at the present time the statement made 
by the governor of Pennsylvania that bichloride of mercury " is a 
household commodity " is altogether too true, particularly of the 
tablets — pounds, if not tons, of which are sold annually for other 
than medicinal purposes. 

A survey of the current price lists of five of the larger manufac- 
turers of pharmaceutical preparations in the United States, presents 
some rather startling information, and suggests a really valid reason 
why tablets of corrosive mercuric chloride may be considered to be 
more important factors in the health and welfare of many members 
of the community than is generally supposed. Perhaps the most 
startling discovery is the fact that not a single manufacturer of 
tablets of corrosive mercuric chloride markets them under a name 
properly indicating the nature of the materials contained therein. 
In the lists referred to we find, under corrosive sublimate, mercuric 
chloride or mercury bichloride, a cross reference to antiseptic tablets 
or antiseptics, and under this heading the several price lists men- 
tioned would present the following composite table : 

A composite list of antiseptic tablets from the current price lists of five leading 

manufacturers. 

Antiseptic disks. — Compressed. Green or white. Corrosive mercuric 
chloride 0.5 gm. with ammonium chloride. 

Antiseptic tablets. — Compressed. White, blue, green, red, or pink. Cor- 
rosive mercuric chloride 0.5 gm. with ammonium chloride. 

Antiseptic tablets. — White, blue, green, or red., Corrosive mercuric 
chloride 0.5 gm. with sodium chloride. 

Antiseptic tablets, alkaline. — White, or pink. Sodium borate, sodium 
bicarbonate, sodium salicylate, sodium benzoate, sodium chloride, oil of euca- 
lyptus, thymol, menthol, oil of gaultheria. 

Antiseptic tablets, alkaline, effervescent: — White or pink (?). These tab- 
lets are superior to those usually sold, which harden with age and dissolve 
with difficulty. 

Antiseptic tablets, alkaline, improved. — White or pink. Formula same 
as alkaline antiseptic tablets with addition of hydrastine hydrochloride and 
sanguinarine nitrate. 

Antiseptic alkaline, improved. — Valuable as an injection in urethritis, 
vaginitis, and all diseases of the urethral and vaginal passages requiring a 
mild antiseptic and deodorant. 

Antiseptic tablets, Bernays, small. — White, blue, or pink. Corrosive mer- 
curic chloride 0.125 gm. with citric acid. 

Antiseptic tablets, Bernays, large. — White, blue, or red. Corrosive mer- 
curic chloride 0.5 gm. with citric acid. 



126 



Sale of Bichloride Tablets. 



i Am. Jour. Pharm. 
1 March, 1914. 



Antiseptic tablets, Bernays, special large. — White or blue. Corrosive 
mercuric chloride 0.45 gm. with citric acid. 

Antiseptic tablets, Clover. — White, blue, or pink. Corrosive mercuric 
chloride 0.45 gm. with citric acid. 

Antiseptic tablets, cyanide. — White or pink. Mercuric cyanide 0.5 gm. 
with sodium borate. 

Antiseptic tablets, detergent. — Sodium bicarbonate, sodium borate, sodium 
salicylate, eucalyptol, menthol, and oil of wintergreen. 

Antiseptic tablets, detergent, improved. — Contain in addition to the in- 
gredients mentioned above, sanguinarine nitrate and hydrastine hydro- 
chloride. 

Antiseptic tablets, diamond. — White, blue, or pink. Corrosive mercuric 
chloride 0.5 or 0.125 gm. with citric acid. 

Antiseptic tablets, external. — White, green, pink, or blue. Corrosive 
mercuric chloride 0.5 gm. with ammonium chloride. 

Antiseptic tablets, La Place. — Corrosive mercuric chloride 0.25 gm. with 
tartaric acid. 

Antiseptic tablets, mercuric bichloride, Young's. — Blue. Nine varieties. 

Antiseptic tablets, mercury cyanide. — White or pink. Mercuric cyanide 
0.5 gm. with sodium borate. 

Antiseptic tablets No. 3. — White or pink. Mercuric cyanide 0.5 gm. with 
borax. 

Antiseptic tablets, St. J. Perry. — White or pink. Mercuric cyanide 0.5 gm. 
with ammonium chloride. 

Antiseptic tablets No. 6. — Very soluble. White or blue. Corrosive mer- 
curic chloride 0.5 gm. with citric acid. 

Antiseptic tablets, potassium permanganate. — Compressed. Five varieties. 

Antiseptic tablets, St. J. Perry. — White or pink. Mercuric cyanide 0.5 gm. 
with borax. 

Antiseptic tablets, tartacid sublimate. — Corrosive mercuric chloride 0.25 
gm. with tartaric acid. 

Antiseptic tablets, Young's. — Blue. Corrosive mercuric chloride." Nine 
varieties. 

Antiseptic tablets, Wilson's. — White, green, pink, or blue. • Corrosive mer- 
curic chloride 0.5 gm. with ammonium chloride. 

The tablets in this list containing corrosive mercuric chloride are 
marketed in 16 varying sizes, 5 different shapes, and 5 different 
colors. Three of the shapes are distinctive and probably proprietary 
in nature. Obviously the most objectionable feature is the con- 
fusion which may arise from the totally misleading name applied to 
tablets containing highly toxic materials. 

The possible abuse arising from the use of a totally misleading 
name for poisonous substances is further emphasized by the state- 
ment recently made by one of the agitators for legislation to provide 
a distinctive shape for " antiseptic tablets." This writer says : " It 
is a known fact that the tablets of corrosive sublimate are very easily 



Am Ma J rh?i P 9i4 m -} Sale of Bichloride Tablets. 127 

procured, and are used to a very large extent as a home remedy, 
hence they are not looked upon as the dangerous agents that they 
really are in the hands of the careless and ignorant." 

Among the many suggestions that have been made to compel 
uniformity in shape and size of tablets of corrosive mercuric chloride, 
we have proposals to have them triangular, coffin-shaped, kidney- 
shaped, and in the shape of a skull, in addition to the various forms 
already in use. Suggestions have also been made to enact laws to 
compel manufacturers to color these tablets red, green, blue, yellow, 
and pink; also to give them a distinctive odor, and to compel their 
being dispensed in a uniform and distinctively shaped bottle ; all of 
which, if it were practicable to enforce uniformity in all States and 
with all manufacturers, would at best tend to elaborate on the 
misuse of tablets of this kind, rather than to prevent accident, or 
their use as a poison for suicidal purposes. 

Even at the present time there is sufficient legislation, if en- 
forced, to serve as a reasonable safeguard in connection with the 
sale of corrosive mercuric chloride at retail. No less than 38 States 
include corrosive sublimate specifically in the laws designed to restrict 
the sale of poisons, and in but one of the existing laws, that of Utah, 
are corrosive sublimate tablets exempted from registration in the 
poison register, otherwise uniformly required for the sale of cor- 
rosive sublimate itself. During the present year, three States, 
Oregon, Nevada, and California, have enacted modified poison laws 
and specifically enumerate tablets of corrosive sublimate as belong- 
ing in " Schedule A," drugs, the sale of which is required to be 
registered in a book provided for that purpose. These several States 
also specifically enumerate " antiseptic tablets containing corrosive 
sublimate," being, so far, the only States recognizing the present-day 
custom of labelling these very toxic preparations, " antiseptic 
tablets." 

In addition to specific agitation for the proper labelling of all 
preparations containing poisonous substances, the most promising 
innovation is the suggestion that a type form of corrosive mercuric 
chloride tablet or pastille be introduced in the Pharmacopoeia of the 
United States, with a view of providing adequate safeguards to pre- 
vent accidental poisonings. While the suggestions that have been 
made for this purpose are many and varied, it would appear that, 
in view of the rapidly growing intercourse between the different 
countries of the world, it might be desirable to secure international 
uniformity in regard to preparations of this type. It has been pro- 



128 



Progress in Pharmacy* 



f Am. Jour. Pharm. 
\ March, 1914. 



posed, unless specific and valid objections could be offered, to adopt 
for inclusion in the Pharmacopoeia of the United States the descrip- 
tion of mercuric chloride pastilles included in the German Pharma- 
copoeia. This latter Pharmacopoeia provides that pastilles of mer- 
curic chloride consist of equal parts of corrosive mercuric chloride 
and sodium chloride, and requires that the pastilles be colored bright 
red with aniline dye, have a cylindrical shape, and be twice as long 
as thick. These tablets or pastilles must be wrapped individually in 
black paper, bearing the German equivalent of the word poison in 
white letters. The weight of a tablet must be stated, and the 
wrapped tablet is to be dispensed only in suitable glass bottles or 
tubes. 

As an argument for including in the Pharmacopoeia of the United 
States an official tablet of corrosive mercuric chloride, rather than 
enacting legislation to compel uniformity in the shape, size, color, 
and odor of all tablets containing corrosive mercuric chloride, it has 
been pointed out that inclusion in the Pharmacopoeia would not in 
any way interfere with the legitimately established trade of manu- 
facturers, but would tend to discourage the sale and use of such 
preparations and bring about the gradual popularization of the 
official tablet. If, in addition to this, it were practicable to induce 
manufacturers properly to label all of their preparations so as to 
indicate the presence of any highly toxic substance, and then to sug- 
gest to purchasers of tablets of this kind the need for keeping them 
apart or in such a way that they could not readily be mistaken for 
other nontoxic preparations, little or no additional legislation would 
be necessary, unless it were to restrict newspapers from publishing 
unnecessary details in regard to the nature and kind of poison used 
in cases of accidental or intentional poisoning. 



PROGRESS IN PHARMACY. 

A Quarterly Review of Some of the More Interesting Litera- 
ture Relating to Pharmacy and Materia Medica. 

By M. I. Wilbert, Washington, D. C. 

An unusual amount of activity is being reflected in current 
pharmaceutical and drug journals. While much of this activity is 
more or less closely related to renewed interest in the revision of 
the Pharmacopoeia, awakened by the publication of the first instal- 



Am. Jour. Pharm. ) 
March, 1914. / 



Progress in Pharmacy. 



129 



ment of Abstracts of Proposed Changes, with New Standards and 
Descriptions to be included in the U. S. P. IX, legislation and the 
prospective meetings of national and state associations are also 
being actively discussed in all sections of the country. 

Looking Ahead. — The editor of the Bulletin of Pharmacy sug- 
gests some reform measures for the A. Ph. A., which deserve the 
careful attention and the hearty co-operation of every member of 
that association. The proposed reforms of immediate interest con- 
cern the coming meeting of the A. Ph. A., more particularly the 
program of section meetings. Not the least important of the sug- 
gestions made is the proposition to have the Council meeting held 
in the evenings so as to eliminate the constantly increasing interfer- 
ence of the Council meetings with the meetings of the sections. 
Another proposition of considerable interest is the suggestion to 
restrict the scientific meetings of the Association sections to two 
sessions a day. The third proposition is to eliminate from the now 
existing sections such as do not warrant continuance and thus restrict 
the scientific business of the Association to simultaneous sessions 
of a limited number of sections for a sufficient number of days to 
transact all of the business in hand. If in addition to these several 
reforms the unnecessary interference by entertainment features could 
be eliminated, there is no reason why the meetings of the American 
Pharmaceutical Association should not be held as are the meetings 
of the American Medical Association, in from 3 to 4 days, allowing 
the additional days of the week for entertainments or for the meet- 
ings of correlated societies and associations that choose to convene at 
or about the same time that the American Pharmaceutical Associa- 
tion does. Mr. Mason truthfully says that the existing trouble with 
the A. Ph. A. " arises from too much energy instead of too little, 
and what is needed is that this energy in its manifold manifestations 
be harnessed up and co-ordinated in a more intelligent manner. 
. . . The situation at Nashville last August was one of confusion 
worse confounded. There were the seven regular sections of the 
Association, each holding two or three sessions. There was the 
annual meeting of the National Association of Boards of Pharmacy 
with four or five sessions. There was the annual meeting of the 
Conference of Pharmaceutical Faculties, and the joint conference 
of the section on Education and Legislation of the A. Ph. A. . 
With it all there was no let-up in the work from nine o'clock in the 
morning until one or two o'clock the next morning. Everybody was 



130 



Progress in Pharmacy. 



{Am. Jour. Pharm. 
March, 1914. 



tired out. Everybody was more or less befuddled by the multiplicity 
of business. . . . The A. Ph. A. has outgrown the clothes of 
a growing youth and now needs the equipment of the adult it has 
come to be. Particularly are the annual meetings in need of reform 
if they are successfully, intelligently and efficiently to handle the 
vast amount of work undertaken by the Association." — Bull. Pharm., 
1 9 14, v. 28, pp. 67-70. 

Drijg Trades' Conference. — A meeting of the National Drug 
Trades' Conference was held at Washington, January 12 to 14, all 
of the several national organizations being represented. Among the 
resolutions adopted by the Conference were : 

One asking newspapers to omit as far as possible all detail of 
poisons or other instruments employed in suicide and murder. 

One recommending that legislation relating to methods of pack- 
ing and labelling of corrosive mercuric chloride tablets and other 
dangerous toxic drugs be deferred, pending a report by the Commit- 
tees of Revision of the Pharmacopoeia and the National Formulary, 
and tendering such aid as the members of the conference may be in 
a position to give in making the revision, in order that suitable regula- 
tion with respect to these drugs may be made. 

One requesting the Postmaster-General to change paragraph 5 
of section 472 of the postal regulations, so as to permit the mailing 
as first-class matter of poisonous substances packed in metal con- 
tainers, bearing the name of the sender and the word " Poison." 

One requesting that the Committee of Revision of the United 
States Pharmacopoeia consider the desirability of inserting in the 
forthcoming revision of the United States Pharmacopoeia a section 
defining the word " poison." — Drug. Circ, 1914, v. 58, p. 99. 

Poison Bottles. — Anon. The use of a special bottle for poisons 
is not enforced by law in the United States, although legislation em- 
bodying the principle has more than once been attempted in various 
States. On what grounds the proposals have been rejected we can- 
not understand, for there is ample proof in the experience of our 
own country that the " poison bottle " is an excellent danger signal. — 
Pharm. J., 19 14, v. 92, p. 89. 

Restriction of Sale of Coal-tar Synthetics. — The Kansas 
City Association of Retail Druggists is conducting an energetic 
movement toward legislation prohibiting the sale of antipyrin, acet- 
phenetidin, and acetanilide, except on physicians' prescriptions. — 
Drug. Circ, 19 14, v. 58, p. 103. 



Am. Jour. Pharm. ) 
March, 1914. f 



Progress in Pharmacy. 



Drug Store Strike. — The advantages of efficient organization 
and co-operation are well emphasized in a recent number of the Phar- 
mazeutische Post (December 24, 1913, v. 46, pp. 1109-1112), which 
publishes an illustrated description of a successful drug store strike 
in Argentine brought about by a proposal to increase the stamp tax 
on specialties and perfumery, and to impose a complicated method 
of control which the druggists of Argentine considered impracticable. 
The strike was general, every drug store in Argentine closing on a 
given date and the concerted action promptly resulted in the law 
being set aside for the time being and subsequently revised. 

Useful Drugs. — An editorial designates the recently published 
volume on Useful Drugs as a book with a purpose that will mark 
an era in American medicine and will likewise have a distinct effect 
upon American pharmacy. The editor criticizes the inclusion of 
syrup of sarsaparilla on the mistaken supposition that its use is 
recommended as a vehicle but concludes that even this is a minor 
matter and Useful Drugs has a purpose and also has a future. — 
Drug. Circ, 1914, v. 58, p. 66. 

In a book review, p. 98, the same journal adds : " Useful Drugs 
can therefore be described as the ideal epitome, and the pharmacist 
interested in his prescription department will do well to aid in the 
circulation of the work by distributing it among physicians of his 
own neighborhood." 

Digest of Comments on the Pharmacopoeia of the United 
States of America. — A book review of Hyg. Lab. Bull., No. 87, says 
in part : " In the period covered by this, the seventh in the series of 
' Digests,' the critical character of the comments on the German Phar- 
macopoeia might be taken to indicate that the makers of pharmaco- 
poeias must in the future cater to a more and more discriminating 
constituency. This attitude on the part of users of pharmacopoeias is 
still further emphasized by the growing demand for a limited materia 
medica and, by inference, the limitation of the scope of the pharma- 
copoeia to substances of recognized therapeutic efficacy and sub- 
stances which, to some degree at least, lend themselves to adequate 
standardization, whether chemical or physiologic. — /. Am. M. Assoc., 
v. 61, p. 2005. 

Japanese Pharmacopoeia. — A new revision of the monographs 
of the Ph. Japon III is announced as taking effect December 27, 1913. 
The changes involve acetylsalicylic acid, lanolin and oil of sandal- 
wood. — Chem. and Drug., 1914, v. 84, p. 167. 



132 



Progress in Pharmacy. 



J Am. Jour. Pharm. 
\ March, 1914. 



Ph. Brit. — The British Pharmacopoeia Committee reports that 
" Two further sections of the text of the new Pharmacopoeia have 
been prepared by the editors, and have been submitted to the Com- 
mittee and to the several Committees of Reference. All the sections 
so prepared have been sent to press and are at present in type, 
undergoing revision. It is hoped that the appendix, and the con- 
cluding parts of the draft, will be ready for consideration early in 
the new year." — Pharm. J., 1913, v. 91, p. 849. 

Pharmacopceal Doses. — An editorial, in commenting on a propo- 
sition, recently made in the Medical Press of Great Britain, to adjust 
the strength of tinctures so that the doses of various groups distin- 
guished by prefixing " per " and " sub " would be the same, says : 
" Pharmaceutical^ the strength of tinctures is only of importance 
when regarded from the point of view of providing sufficient men- 
struum adequately to exhaust a drug." " In regard to the sugges- 
tion as to names the question arises in connection with subtinctures, 
will the alcohol or the drug in the tincture be the more grateful and 
comforting to the patient?" — Chem. and Drug., 1914, v. 84, pp. 
19-20. 

Proprietary Medicines in Great Britain. — Xrayser II, com- 
menting on the first year of medical benefit under the insurance act in 
Great Britain, asserts that it has brought with it a marked change 
in the nature of business done by chemists and druggists. One man 
reports that he will dispense 10,000 prescriptions and upon the whole 
he is satisfied from the profit realized directly from this source. The 
increase in the prescription business is further notable for the fact 
that the trade in proprietaries has considerably decreased and should 
mean that chemists as a whole are enjoying, and will continue to 
enjoy, the increase in what is after dispensing the most profitable 
department of their business. — Chem. and Drug., 19 14, v. 84, p. 85. 

Historical Medical Museum. — An unsigned article presents a 
number of illustrations of the Historical Medical Exhibition in Wig- 
more Street, London, which was organized by Henry S. Wellcome 
and opened on the occasion of the International Medical Congress dur- 
ing last summer. This museum is now being rearranged as a perma- 
nent institution and there is probably nothing in existence elsewhere 
which is quite like the collection which will shortly be available for 
the use of students and others interested in the study of antiquarian 
medicine and surgery. The illustrations include a reproduction of 
the exterior of a London apothecary's shop of the 17th Century, 



Am. Jour. Pharm. \ 
March, 1914. J 



Progress in Pharmacy. 



133 



" At the sign of ' Ye wild man/ " a reproduction of Liebig's 
laboratory at Giessen, and the interior of an Italian pharmacy of 
the 1 6th Century. — Pharm. J., 191 3, v. 91, pp. 944-945. 

History of Pharmacy. — The Chemist and Druggist, January 31, 
1 9 14, v. 84, p. 183, announces that an arrangement has been made 
with the publishers of the " Chronicles of Pharmacy," by the late 
A. C. Wooton, which enables that journal to offer this book in two 
volumes at 7s. 6d., carriage paid in the United Kingdom, or 8's. post 
free to any part abroad. This exceptional offer should popularize 
the book and make it available to all pharmacists who are in any 
way interested in the history of their craft. Orders for the volumes 
should be addressed to the book department of the Chemist and Drug- 
gist, 42 Cannon Street, London, E. C. 

Friedmann Institutes are being organized in various parts of 
the country and the personnel of these organizations in practically 
every instance is sufficient to suggest their true nature. Steps have 
been taken in several states to check this exploitation of the consump- 
tive for commercial gain. But what is most needed is that these 
unscrupulous attempts should be met with an intensive campaign 
of education of the public concerning the dangers and worthlessness 
of this treatment. — /. Am. M. Assoc., 1913, v. 61, p. 1050. 

U. S. Patent for a Complex Medicine. — An editorial calls at- 
tention to U. S. Patent 1,081,069, granted December 9, 191 3, for a 
mixture of excretory constituents — creatinin, guanidin, and allan- 
toin — to be used as a specific in a number of microbial infections 
and illnesses. The editorial states that the granting of a patent on 
the claims made should be sufficient to show the need of change in 
the method of granting patents, at least in the methods governing 
the issuance of patents for medicinal products. — /. Am. M. Assoc., 
1914, v. 62, pp. 54-55. 

Aloes. — Tutin and Naunton report an investigation to ascertain 
if any anthraquinone derivative other than aloe-emodin is contained 
in aloes. They were unable to isolate such compounds as emodin 
and chrysophanol but found several samples of aloes which contained 
aloe-emodin as an impurity. — Pharm. J., 1913, v. 91, p. 836. 

Alypin, Misleading Advertisement of. — Bruck, F., called at- 
tention four years ago to the misleading statements in the advertising 
of alypin. Both an anaesthetic and blood-expelling action are claimed 
for it but in reality it has none of the latter. It is also stated that 
alypin is considerably less toxic than cocaine, while Schroder and 



134 



Progress in Pharmacy. 



f Am. Jour. Pharm. 
\ March, 1914. 



others have found that it is fully as toxic as cocaine and the last sup- 
plement to the German Pharmacopoeia gives the maximum dose the 
same for both alypin and cocaine. — Therap. Monatsh., Berlin, 1913, 
v. 27, p. 787. 

Arheol is a proprietory name for santalol, C 15 H 26 OH, a sequi- 
terpenic alcohol, the chief constituent of sandalwood. Arheol is 
a colorless, oily liquid; specific gravity, 0.979 at 15 C. It is in- 
soluble in water but soluble in alcohol. It boils under 1 1 mm. pres- 
sure at 169 , and under ordinary pressure at about 500 C. — /. Am. 
M. Assoc., 1913, v. 61, p. 1900. 

Atophan, Secondary Effects of. — Phillips, John, calls attention 
to the occurrence of various skin rashes caused by the administra- 
tion of atophan and reports 5 cases. These rashes resemble those 
following the administration of antipyrine and indicate that atophan 
should not be given in the treatment of urticaria as has been advised. 
— /. Am. M. Assoc., 1913, v. 61, p. 1040. 

Behring's Diphtheria Vaccine. — Kissling, K., reports on the 
application of Behring's new vaccine to immunize children who had 
been exposed to diphtheria in different wards of the Hamburg 
general hospital. Of the 310 children treated, 111 were given a sec- 
ond injection and none of this group has contracted diphtheria, and 
only 8 among the remaining 199. In these cases the patients were 
convalescing from scarlet fever and the diphtheria was exceptionally 
mild, or the vaccine did not have time to act before the diphtheria 
developed ; several days are required for the vaccine to complete 
the immunization. Adults respond with more of a reaction to the 
vaccine than children. Pre-existing disease of any kind does not 
seem to be a contra-indication. (Deutsch. med. Wchnschr., 1913, 
v. 39, No. 51.) — /. Am. M. Assoc., 1914, v. 62, p. 418. 

Cereus Grandiflorus. — Grober, A. Many contradictory state- 
ments have been published as to the activity of Cactus grandiflorus 
and its value as a heart remedy. The pharmacological experiments 
of the author show that the drug exerts some action on the frog's 
heart similar to digitalis. This may be attributed to the glucoside 
present as well as to the alkaloid. The amount of active principles 
present in the drug is, however, so small, that it cannot be consid- 
ered in any way as a substitute for digitalis in human therapeutics. — 
Therap. Monatsh., 1913, v. 27, pp. 580-581. 

Chromium Sulphate. — Kolipinski, S., is quoted as saying: 
" The diseases in which chromium has been used with success are : 



Am. Jour. Pharni. ) 
March, 1914. / 



Progress in Pharmacy. 



135 



cirrhosis of the female breast, castration, menopause, functional im- 
potency in men, chronic alcoholism, nervous vomiting and vomiting 
in pregnancy, neurasthenia, locomotor ataxia, exophthalmic goiter 
and the migraines." — /. Am. M. Assoc., 19 13, v. 61, p. 192 1. 

CUNILA MARIANA L., A SUBSTITUTE FOR SpIGELIA. StOCk- 

berger, W. W. Several samples offered as pink root, recently sub- 
mitted by dealers in crude drugs, were found on investigation to be 
spurious and to consist largely of Cunila mariana L. — /. Am. Pharm. 
Assoc., 1914, v. 3, pp. 33-34. 

Cusylol. — Cusylol is a soluble form of copper citrate, intro- 
duced for use in ophthalmic work. It is a blue crystalline powder, 
soluble about 1 : 3 in water. The powder is stable. Solutions above 
1 : 1,000 in strength do not keep well, since they attack some kinds 
of glass with the formation of a flocculent deposit. — Pharm. J., igi4, 
v. 92, p. 136. 

Digipan, according to the manufacturers, represents, with the 
exception of digitonin, all of the glucosides of digitalis leaves, 
obtainable by extraction at not exceeding 30 . — Sudd. Apoth.-Ztg., 
1913* v. 53, p. 833. 

Diogenal is a new sedative related to veronal. Chemically it is 
dibrom-propyl-diethyl-barbituric acid, C 11 H 16 Br 2 N 2 2 . It is a white 
crystalline powder melting at 126 . The average dose is 15 grains. — 
Chem. and Drug., 1914, v. 84, p. 37. 

Echinacea. — Anon. Echinacea has been claimed to be a 
" specific " for rattlesnake bite, syphilis, typhoid fever, malaria, diph- 
theria and hydrophobia. Later enthusiasts have credited it with 
equally certain curative effects in tuberculosis, tetanus and exoph- 
thalmic goiter, and with power of retarding the development of can- 
cer. On the basis of the available evidence the Council on Pharmacy 
and Chemistry decided that echinacea was not worthy of recognition 
as a drug of probable value. Accordingly it voted not to describe 
the drug in New and Non-official Remedies ( The Journal, Nov. 27, 
1909, p. 1836). So far as can be learned no reliable evidence for the 
claims made for this drug has been presented since the Council de- 
cided that the available evidence did not entitle it to a place in New 
and Non-official Remedies. — /. Am. M. Assoc., v. 61, p. 2089. 

Elarson is the strontium salt of chlorarsenobehenolic acid, con- 
taining about 13 per cent, of elementary arsenic and about 6 per 
cent, of chloride. It occurs as an almost white, amorphous, tasteless 
powder, insoluble in water but slightly soluble in alcohol and ether. 



136 



Progress in Pharmacy. 



f Am. Jour. Pkarm. 
\ March, 1914. 



The average adult dose of elarson is 0.008 gm. grain), three to 
five times daily, best taken about an hour after meals. — /. Am. M. 
Assoc., 1914, v. 62, p. 379. 

Emetine Hydrochloride. — Korns, John H. Emetine hydro- 
chloride is the approved method of treatment for amoebic dysentery 
among missionary physicians in China. In a recent report of 17 
cases, 16 did well under the emetine treatment, the 1 exceptional 
case had been treated unsuccessfully with ipecac powders six months 
previously. — /. Am. M. Assoc., 1914, v. 62, p. 475. 

Ergot, according to Lieb, owes its pharmacologic action to sev- 
eral constituents ; of these, ergotoxine alone is specific. Beta-imi- 
doazolyethylamin, parahydroxyphenylethylamin, and the other sym- 
pathoninetic amines are products of the putrefaction which occurs 
during the manufacture of galenical preparations. Each constituent 
has a distinct pharmacologic action ; stimulation of the uterus is 
characteristic of them all. — /. Am. M. Assoc., 1914, v. 62, p. 486. 

Fucitol. — Votocek and Potmesil. Fucose, the sugar obtained 
from bladder-wrack, Fucus vesiculosus, when reduced with sodium 
amalgam, is converted into the alcohol fucitol. This new alcohol 
crystallizes from ethyl alcohol in silvery leaflets which melt at 153- 
154 C. Rhodeose and fucose are stereo-isomers, and the corre- 
sponding alcohols, fucitol and rhoditol, are respectively laevo- and 
dextro-rotary to the same degree. By mixing the two alcohols in 
equimolecular proportions in hot alcohol, racemic fucitol is obtained. 
(Berichte, 1913, v. 46, p. 3653.) — Pharm. J., 1913, v. 91, p. 911. 

Gitonin. — Windhaus and Schneckenburger have recently separ- 
ated a new digitalis glucoside from Kiliani's digitonin. Digitonin 
was dissolved in hot alcohol, 95 per cent. On setting aside the solu- 
tion for some weeks an amorphous deposit was formed containing 
the new glucoside. Gitonin is but sparingly soluble in water, in 
methyl, and in ethyl alcohols. It is insoluble in acetone and in ether. 
It becomes yellow when heated to 255 C. and decomposes at about 
272 C. With sulphuric acid it gives at first a pink, then a red color. 
The exact formula of the glucoside has not yet been determined ; 
provisionally it is given as C 29 H 80 O 2V — Pharm. J., 1913, v. 91, p. 911. 

Hediorite is the lactone of a-glucoheptonic acid. It is recom- 
mended, to the extent of 30 gms. per diem, for diabetic patients. 
It forms crystals melting at 145 to 148 °, easily soluble in water. — 
Chem. and Drug., 1914, v. 84, p. 89. 

Hydroxyphenylethylamin. — The pharmacologic investigation 



Am. Jour. Pharm. ) 
March, 1014. _ J 



Progress in Pharmacy. 



137 



of synthetic aromatic amines has been greatly stimulated by the dis- 
covery of the chemical structure of epinephrine and the demonstra- 
tion that it belongs in this group of organic compounds. The syste- 
matic testing of numerous related and suitably constituted amines 
has shown that in general they exhibit pressor effects on the circu- 
lation and other physiologic phenomena characteristic of the effective 
agent of the adrenals, their activity increasing according as they 
approach the chemical structure of epinephrine. One of the most 
interesting of all these newly investigated products is hydroxyphenyl- 
ethylamin, which can readily be prepared from the protein cleavage 
derivative ty rosin by splitting off carbon dioxide from the molecule 
of the latter. This reaction can be brought about by putrefactive 
bacteria ; and in truth hydroxyphenylethylamin has been detected 
among the products of putrefaction of proteins and identified by 
Barger among the pressor principles yielded by putrid meat. — /. Am. 
M. Assoc., 1914, v. 62, p. 46. 

Lactic Acid Ferments. — Puckner, W. A. The frequently 
made assertions that the lactic acid preparations on the market are 
worthless, led to an examination of the available commercial prod- 
ucts. This examination showed that while all products containing 
living bacteria are bound to deteriorate, the preparations examined 
were in viable condition, though, as was to be expected, liquid cult- 
ures were more active than were the tablet preparations. It was also 
found that manufacturers of these products are making every effort 
to insure the dispensing of reliable preparations when they are 
ordered by physicians. — /. Am. M. Assoc., 191 3, v. 61, p. 2084. 

Liquid Paraffin. — Peck, J. Wicliffe, calls attention to the wide- 
spread use of liquid paraffin for chronic constipation, in different 
sections of Great Britain, and to the possibility of developing the sale 
of this article as a specialty. He also points out that there is a great 
difference in the viscosity of the many samples obtained and that it is 
preferable to use one having a medium specific gravity. The more 
fluid ones are not so useful in the treatment of intestinal stasis and 
the heavier preparations are apt to be objectionable because they 
do not easily leave the mouth. — Pharm. J., 19 14, v. 92, pp. 28-29. 

Liquid Paraffin. — Chrysopathes, J. G. During the Balkan war 
920 cases of wounds were dressed with liquid paraffin. In nearly 
every case the wound healed over in a remarkably short time ; even 
gaping wounds with exposed bones began to heal at once. The oil, 
in fact, is recommended as a dressing for sores of all kinds, and 



i3« 



Progress in Pharmacy. 



( Am. Jour. Pharm. 
\ March, 1914. 



where there is severe suppuration the addition of 2 per cent, of iodo- 
form improves matters. (Zentralbl. filr Chirurg., Leipsic, Novem- 
ber 8, 1913.) — Pharm. J., 1914, v. 92, p. 6. 

Opium. — Mr. Jewel, the American Consul at Vladivostok, re- 
ports that poppy culture was introduced into the Ussuri district by 
Chinese, and in 1907 the exports to China amounted to 7223 lbs. 
This has since increased. — Pharm. J., 1914, v. 92, p. 79. 

Organic Silver Salts. — Rogers, L. With the exception of 
argyrol, all of the organic silver compounds tested had a decided 
bactericidal action against the dysentery bacillus when dissolved in 
water, being effective in five minutes in dilutions of 1 in 2500 and 
upwards. In the presence of a little broth, however, their action was 
always weaker, but in a variable degree. — /. Am. M. Assoc., 1914, 
v. 62, p. 412. 

Perhydrit is a combination of hydrogen peroxide with urea, 
marketed in the form of 1 gm. tablets representing from 0.34 to 0.35 
per cent, of hydrogen peroxide and therefore a solid form of hydro- 
gen peroxide which when dissolved in water may be used as a disin- 
fectant. — Si'idd. Apoth.-Ztg., 191 3, v. 53, p. 841. 

Phenolsulphonephthalein is a product of the interaction of 
phenol and sulphobenzoic acid anhydride, differing from phenol- 
phthalein in that a CO group of the latter is replaced by a S0 2 group. 
Phenolsulphonephthalein is used for determining the functional 
activity of the kidney. When injected intramuscularly or intra- 
venously it begins to be excreted in normal cases in from five to ten 
minutes. In cases of a deficient functional activity, the first appear- 
ance of its secretion is delayed. — /. Am. M. Assoc., 1914, v. 62, 
pp. 297-298. 

Phenoval is a-brom-isovaleryl-paraphenetidin, (CH 3 )2CH.- 
CHBr.CO.NH.C 6 H 4 .OC 2 H 5 . It is a new crystalline compound melt- 
ing at 149 to 150 , and is recommended as sedative and hypnotic. 
It is insoluble in water, but is soluble in the usual organic solvents. 
Its dose is from 0.5 to 1.0 gm. — Chem. and Drug., 1914, v. 84, p. 89. 

Pikrastol, administered in cases of epilepsy, is dimethyloldi- 
formyl-methyleneyl-tetramethylene-pentamine, C 9 H 17 N 5 4 . It is 
amorphous, and does not appear .fo have a well-defined melting 
point. — Chem. and Drug., 1914, v. 84, p. 37. 

Quinine. — MacGilchrist, A. C, claims that precipitated quinine 
base is the best all-round form in which to administer quinine by 
mouth ; it can be administered intravenously, and it is preferable to 
any quinine salt in cases in which hemoglobinuria is dreaded. (Ind. 



Am. Jour. Pharm. ) 
March, 1914. / 



Progress in Pharmacy. 



139 



/. Medical Research, 1913, v. I, No. 2.) — /. Am. M. Assoc., 1914, 
v. 62, p. 413. 

Quinine and Urea Hydrochloride. — Cables, H. A., reports 
eight cases of sciatica treated by hypodermic injections of a four 
per cent, solution of quinine and urea hydrochloride in normal salt 
solution. There were 50 injections in all, but no untoward results 
other than a little soreness that always follows hypodermic injections. 
Seven patients received six injections each and one received eight. — 
/. Am. M. Assoc., 1913, v. 61, p. 2303. 

Rabies and the Pasteur Treatment. — Anon. The work of 
Pasteur drew the attention of the medical profession and the laity 
to rabies, which up to that time had apparently been neglected. The 
fatality among Pasteur-treated patients is less than 1 per cent., while 
the death-rate for all persons bitten by rabid animals is considered 
to be from 15 to 20 per cent. — /. Am. M. Assoc., 1913, v. 61, p. 1923. 

Radium. — A recent census of the quantity of radium salts at pres- 
ent in the various laboratories of the world shows that this does not 
exceed the equivalent of 7 gms. of metallic radium. From 1899 to 
1904, from 13 tons of pitch-blende residuum, it was possible to 
extract only 2 or 3 gms. of radium. Then a stop was put by law 
to the export of radiferous material from Austria. Radium has 
since been extracted in France from much poorer ores containing 
only from y 2 to 2 mgms. per ton, whereas the Austrian pitch-blende 
contained quite 100 times as much. Besides its use in medicine, its 
application in the industries is spreading. Radium has been used in 
silk factories for de-electrifying the material and the machines. It 
is possible to realize, with radium, an apparatus for measuring from 
a distance the potential of a conductor, without contact. — Pharm. J., 
1913, v. 91, p. 938. 

Radium in Australia. — Anon. Important radio-active minerals 
are stated to have been discovered at two places in South Australia. 
In one of these cases the material as a whole did not contain sufficient 
uranium and vanadium to be of commercial importance in the crude 
state, but results of considerable scientific interest are said to have 
been obtained in the course of the inquiry. The composition of an- 
other radio-active ore in South Australia has also been determined. — 
Pharm. J., 1914, v. 92, p. 115. 

Saffron. — Holmes, E. M., in a review of the varieties of saf- 
fron, points out that although this plant is cultivated in most of the 
large countries for home use, it is exported from very few and its 
adulteration from the time of Pliny to the present day expresses 



140 



Progress in Pharmacy. 



J Am. Jour. Pharm. 
| March, 1914. 



to some extent its scarcity. For more than iooo and probably 2000 
years saffron has held its own as a medicine and as an ingredient in 
food, and it is hardly to be supposed that this would be the case if it 
possessed no useful properties. — Pharm. J., 1913, v. 91, pp. 941-943. 

Salvarsan. — Editorial. In salvarsan and neosalvarsan reliance 
is placed in combinations of arsenic of complex molecular structure. 
In this form the arsenic is relatively non-toxic, but as in the case 
of many other compounds, the biochemical agencies of the body may 
split the complex chemical structures into simpler ones, reducing 
the non-toxic combinations into products which may be highly toxic 
to the tissues of the human organism. So long as we are not able 
to predict with certainty what chemical reactions may take place 
within the body under various conditions, there will remain more or 
less risk connected with the administration of drugs so potentially 
toxic as are these higher compounds of arsenic. For future guid- 
ance, all instances of unfavorable outcome after their use should be 
recorded in detail with great care. — /. Am. M. Assoc., 1913, v. 61, 
p. 2074. 

Permanent Scopolamine Solution. — The presence of the 
higher alcohols, such as mannitol or dulcitol, in solutions of scopola- 
mine, renders them more permanent, and the use of these for this 
purpose is the subject of a German patent. — Pharm. J., 1913, v. 91, 
P- 943- 

Siam Benzoin. — Holmes, E. M., gives an interesting summary 
of the efforts that have been made in the last 50 or 60 years to find 
the botanical source of Siam Benzoin. The evidence adduced seems 
to indicate that the chief, if not the only source of the Siam Benzoin 
of commerce, is Styrax Tonkinense, Craib, which is found in the 
district between Luang Prabang and Hanoi ; second, that the Styrax 
benzoides of Northwest Siam yield a fragrant resin, used locally, 
but the evidence that it yields any of the Siam benzoin of commerce 
is not equally satisfactory. — Pharm. J., 1913, v. 91, pp. 804-806. 

Spirit of Nitrous Ether. — Hodgson and Bailey report tests 
to determine how far the defense usually set up in prosecutions is 
justified. Results show that spirit of nitrous ether retains its 
strength remarkably well if kept in small, tightly stoppered bottles 
and not opened too frequently. — Pharm. J., 1914, v. 92, p. 28. 

Syrups, Fermentation of. — Cochran and Perkins report an in- 
vestigation on the influence of small amounts of ethyl alcohol on fer- 
mentation in cane sugar syrup, and conclude : 



Am. Jour. Pharm. ) 
March, 1914. / 



Progress in Pharmacy. 



1. One per cent, or less of alcohol markedly accelerates fermen- 
tation in syrup of average densities. 

2. 1.25 per cent, alcohol has very little influence. 

3. Beginning with 1.25 per cent, the presence of alcohol retards 
fermentation in these syrups, the amount of retardation increasing 
with the increase in the percentage of alcohol. — /. Ind. and Eng. 
Chem., 1914, v. 6, p. 141. 

• Theoform. — A condensation product of theobromine with a for- 
maldehyde-liberating substance has been put on the market under the 
name of theoform. It is claimed to contain 85 per cent, of theobro- 
mine, and is therefore richer in that base than diuretin or agurin. A 
white, bitter powder, soluble 1 : 50 in water at ordinary temperatures, 
but is not stable in neutral or alkaline solution. — Pharm. /., 1914, 
v. 92, p. 62. 

Thymolphthalein occurs in colorless needles, melting at 245- 
246 C. ; readily soluble in alcohol and in acetone ; sparingly dissolved 
by chloroform or by ether. It dissolves in caustic alkalies with the 
formation of a blue color; it may therefore serve as an indicator for 
alkalimetry, for the color is not affected by excess of alkali. — 
Pharm. 1913, v. 91, p. 881. 

Thyroideum Siccum. — Bennett, Reginald R., discusses the rela- 
tive weight of dried and of fresh thyroid gland, and questions the 
frequently made statement that 1 part by weight of the dried thyroid 
represents 5 parts by weight of the fresh thyroid. Some observa- 
tions of his own lead him to believe that the relation is more nearly 
1 to 4. — Pharm. J., 191 3, v. 91, p. 804. 

Tyrene. — Para-iodo-ortho-sulpho-cyclo-hexa-triene pyridine is 
conveniently shortened for ordinary purposes to tryene. An odor- 
less, non-toxic powder, soluble in hot water, it is introduced as an 
antiseptic. Specially recommended for use in gynaecology and as a 
dressing for wounds, either as a dusting powder, gauze or on tam- 
pons. — Phanm. J., 1914, v. 92, p. 62. 

Ulsanin. — Described as " hydroiodoborate," is put forward as 
a new non-poisonous but active disinfectant and healing application 
for the treatment of wounds. It is a somewhat hygroscopic powder, 
which, in contact with wound secretions, liberates iodine and oxygen. 
— Pharm. J., 1913, v. 92, p. 102. 

Vaccine. — Anon. The virus of variola and of vaccinia is less 
sensitive to the action of glycerin than bacteria in general, and for 
this reason it is possible to obtain an almost pure virus of practically 



142 



Book Review. 



f Am. Jour. Pharm. 
\ March, 1914. 



full strength. Prolonged action of the glycerin, however, destroys 
the virus, but more rapidly at 37 C. than in the cold ; if kept at from 
— 5° to — 15 C. glycerinated virus may remain active for five years. 
— /. Am. M. Assoc., 1913, v. 61, p. 2074. 

" Zymase " in Fermentation Tests. — Rosenbloom, Jacob. The 
zymase of yeast can readily be separated by grinding compressed 
yeast in a mortar with water and sand and adding the expressed liquid 
to 5 times its volume of alcohol. The precipitate is allowed to settle, 
filtered and washed with alcohol followed by ether. The precipitate 
is then dried and preserved in tightly corked amber bottles. Enzyme 
in this form is still active five months after its preparation. — /. Am. 
M. Assoc., 1914, v. 62, p. 377. 



BOOK REVIEW. 

E. Merck's Annual Report of Recent Advances in Pharma- 
ceutical Chemistry and Therapeutics. 1912. Volume xxvi. 

It is not only a pleasure, but pleasure combined with profit to 
read this annual report devoted to pharmaceutical chemistry and 
therapeutics; profitable because it keeps one in touch with current 
literature, and particularly literature from foreign sources, that em- 
braces these two branches of pharmacy and medicine. This is clearly 
evidenced in the first article which in quite an exhaustive manner 
deals with Lecithin, 50 pages being required to deal with this organic 
compound which is so widely distributed in the human and animal 
organisms, and 21 pages containing references to the literature con- 
sulted, making a total of 71 pages. 

Preparations and drugs mainly chemicals, and more particularly 
the action of synthetic chemicals, are commented upon as to their 
advantages and disadvantages when introduced into the human 
economy. When attention is called to the fact that this information 
requires 401 pages one can readily perceive what a wide field is 
covered. 

Organotherapeutics is covered very thoroughly and many in- 
teresting things are brought to light in connection with this form of 
medication. 

A supplement to the report contains a very informative paper by 
Professor Dr. R. Heinz, Director of the Pharmacological Institute 
of the University of Erlangen on " The Assay and Standardisation 
of Digitalis Preparations." j 0HN K Thum 



Am. Jour. Pharm. ) 
March, 1914. / 



Current Literature. 



143 



CURRENT LITERATURE. 

The Bad Taste in Hypochlorite-treated Water-supplies. — 
It is surprising, as pointed out by Lederer (Proc. III. W ater Supply 
Assn., 1913, p. 235), that so little attention has been paid to the 
question of removing the taste from water-supplies treated with 
chlorinated lime. In this country, especially, where the treatment 
of many large public supplies has been carried out with brilliant 
sanitary success, there has been frequent and often bitter complaint 
about the taste of the treated water. As well known, antagonism has 
developed in many places between water boards and health depart- 
ments as a result of these conditions. On one side is the recognition 
that the danger from water-borne diseases is greatly reduced by 
hypochlorite treatment: on the other is the necessity of having to 
bear the burden of daily complaint and to meet the indignant protests 
of thousands of aggrieved water-drinkers. As pointed out by 
Lederer, a simple method is available for removing the taste from 
hypochlorite-treated water. After careful experimenting he has 
confirmed the advantage of sodium thiosulphite (Na 2 S 2 3 , 5H 2 0) as 
recommended by Bruns. The reaction on the residual chlorin is as 
follows : Na 2 S 2 3 + 8C1 + 5ILO = Na 2 S0 4 + H 2 S0 4 + 8HC1. The 
acids formed in the neutralization process immediately combine with 
bases to form neutral salts. Lederer has obtained good results in the 
elimination of taste in Lake Michigan water treated in this way. 
Sodium thiosulphate seems to possess - marked advantages over 
sodium sulphite. It must be remembered that the action of the 
thiosulphate stops the germicidal action of the chlorin so that it is 
necessary to allow the chlorin to act for a sufficient length of time 
(Lederer recommends from at least ten to fifteen minutes) before 
the thiosulphate is added. An interesting point brought out in the 
discussion of Lederer's paper is that hypochlorite seems under 
some conditions to accentuate an unpleasant taste originally 
present in the water. In Toledo, for instance, it is stated that the 
water develops a disagreeable taste when the river first freezes over, 
owing to the presence of large amounts of vegetable matter in the 
water. The bad taste is said to be increased by even small amounts 
of hypochlorite. — Jour. A. M. A., vol. lxi, No. 16, October 18, 1913, 
p. 1464. 



144 



Current Literature. 



{Am. Jour. Pharm. 
March, 1914. 



Studies in Carbohydrates, The Composition and Digesti- 
bility of Wheat Bread and Allied Foods, Gelatinization of 
Starches. — In this paper, by Charles H. LaWall, Ph.M., and Sara 
Graves, B.A., published in Part 2 of the Transactions of the Wagner 
Free Institute of Science of Philadelphia, are given tabulated observa- 
tions of the microscopical characteristics of the following starches : 
Potato, Maranta, Sago, Tapioca, Sweet Potato, Corn, Wheat, Buck- 
wheat, Oat, Rice, Barley, Pea and Bean in the raw state and after 
having been heated in water to 37 , 8o°, and ioo° C. respectively, 
and also after having been subjected to these several temperatures 
for a period of 30 minutes. Gelatinization points for the various 
free starches as well as in pastes made from the crushed materials 
would indicate that in the crushed material the gelatinization points 
are slightly higher. 

Microscopic studies of the starch as found in bread and crackers, 
notably in Acme, Freihofer, Sharpless, and Jones breads and in 
Exton, Sunshine, Educator and Uneeda Crackers, Rolls, Pretzels, 
and Matzoth are tabulated. 

Comparisons of the analyses of the several breads and' crackers 
as given would indicate but very slight differences in these products. 

From a comparison of the ten tables included in this paper it is 
apparent that the food values of the various makes of bread and 
crackers vary only within very narrow limits and that these varia- 
tions are largely due to temperature differences. 

Philip F. Fackenthall. 

Pleads for Drug Users. — A plea for the relief of drug victims 
was made by Dr. Charles A. Towns, of New York, at a legislative 
hearing in the New York Legislature at Albany on February 25, on 
bills designed to restrict the sale of habit- forming drugs, principally 
cocaine and its derivatives. A feature of the proposed laws is a pro- 
vision designed to treat those who obtain drugs in violation of the law 
as victims of disease and not as criminals. This provision would give 
a magistrate authority to commit habitual users of drugs to hospitals 
or sanatoriums instead of prison. 



THE AMEBIC AN 



JOURNAL. OF PHARMACY 




The micro-crystalline active principle of the suprarenal glands, 
Adrenalin, is quite stable when chemically pure. Since it is a pure 
principle with a definite chemical formula 1 the powder does not 
readily decompose when kept under ordinary conditions. However, 
because of its comparative insolubility in water and its great physio- 
logical activity, the preparation most suitable for therapeutic use 
is a i in iooo solution of Adrenalin Chloride, which is an addition 
product formed by the action of dilute hydrochloric acid upon 
Adrenalin. In dilute solutions such as this, the Adrenalin Chloride is 
readily oxidized, if no preservative is added to the solution and it 
is exposed to the air. The oxidation and consequently the deteriora- 
tion of the solution is recognized by the fact that the solution becomes 
pink, then red and finally brown in color. 

Due to this tendency to deteriorate by oxidation, it is claimed 
that a dilute solution of Adrenalin such as a I in iooo solution would 
not withstand sterilization by boiling since the heat would naturally 
tend to hasten the oxidation greatly. The solution is sterile when 
put on the market, but many physicians wish to make doubly sure 
by sterilization immediately before use. 

The following experiments were carried out with the intention 
of determining first, how many times a solution of Adrenalin Chlo- 
ride may be sterilized in a variety of ways without deterioration, 
and second, the relative stability of such a solution compared with 
that of a solution of a synthetic product. The latter, with analogous 
properties and identical composition, is claimed 2 to be more stable 
than Adrenalin which is obtained from the suprarenal glands. 

(i45) 



146 Sterilisation of Adrenalin Solutions. { Am Xp? 1 ? | r 'i9i h 4 arm ' 

First Series. 

In the first experiment 12 ampoules of Adrenalin Chloride Solu- 
tion 1 in 10,000 were used. The method of standardization of the 
solutions which was used in this as well as in all the following ex- 
periments was the blood pressure method 3 in which the solution to 
be tested is diluted till the Adrenalin Chloride content is 1 in 100,000. 
This dilution is then tested in comparison with a 1 in 100,000 solu- 
tion which is made up from an accurately weighed amount of C. P. 
Adrenalin crystals. One ampoule in this series was used as a 
control and its activity found to be equal to standard. The other 
eleven were placed in boiling water, one ampoule being removed 
at the end of each 15 minutes and tested. Each was found to be of 
standard activity. 

This experiment serves to show that the activity of Adrenalin 
Chloride Solution in ampoules is not impaired by sterilizing in boil- 
ing water for any period of time up to 3 hours. 

Second Series. 

A second lot of ampoules of Adrenalin Chloride Solution was 
used, one ampoule as before being reserved as a control. The 
others were sterilized for periods of 15 minutes each and one was 
removed and tested after each sterilization. 

The ampoules for further sterilization were cooled to room tem- 
perature before being sterilized again and the process was not 
repeated oftener than twice a day so that considerable time elapsed 
between two sterilizations. 

Results were as follows : 



Ampoule. Sterilized. Activity. 

No. i Not sterilized Standard 

No. 2 Once (15 min.) Standard 

No. 3 Twice Standard 

No. 4 3 times Standard 

No. 5 4 times Standard 

No. 6 5 times Standard 

No. 7 6 times Standard 

No. 8 7 times Standard 

No. 9 8 times 90 per cent. 

No. 10 9 times 80 per cent. 

No. 11 10 times 80 per cent. 

No. 12 11 times 80 per cent. 



Am Aprii r 'i9u rm ' } Sterilisation of Adrenalin Solutions. 147 

These results show that ampoules of Adrenalin Chloride Solu- 
tion can be sterilized a number of times (in this series 7 times) 
without any deterioration, and after that the loss of activity is 
gradual. 

Third Series. 

The next experiments give a comparison of the stability of 
Adrenalin Chloride Solution 1 in 1000 with that of an analogous 
synthetic substance of equal physiologic activity. The latter was 
made by treating the crystals with dilute hydrochloric acid and 
diluting 1 in 1000. The Adrenalin Chloride Solution used was made 
from C. P. Adrenalin crystals and contained no preservative other 
than a slight excess of hydrochloric acid. This solution was tested 
and found to possess standard activity. 

Three different procedures were followed in sterilizing the 
solutions but the conditions were duplicated for each solution in 
order to obtain a direct comparison. The conditions to which the 
solutions were subjected will be briefly stated and the results placed 
in the form of a table so as to give a better opportunity for com- 
parison. 

In the first method of this series 10 c.c. of the 1 in 1000 solu- 
tion to be sterilized was placed in a graduated cylinder which was 
then plugged with cotton, and gradually heated in a water bath to 
the temperature of boiling water. This temperature was main- 
tained for 15 minutes and at the end of that time the solution was 
cooled, made up to its original volume if any loss due to evaporation 
had occurred, and one cubic centimeter removed for testing. This 
process was repeated four times. 

In the second method 25 c.c. of the solution to be sterilized 
was placed in a tightly corked bottle which was then partially im- 
mersed in boiling water for periods of 15 minutes each. Under 
these conditions there was no loss by evaporation. Each solution 
was submitted to four periods of sterilization and a test of its 
activity made after each period. 

In the third method of this series 20 c.c. of the solution to 
be tested was placed in a small open flask and boiled over a flame 
for 5 minutes. After each period of boiling the loss due to evapora- 
tion, which was considerable, was made up with distilled water and 
the activity of the solution then determined. 



148 



Sterilisation of Adrenalin Solutions. 



\ Am. Jour. Pharm. 
t April, 1914. 



The results of the above experiments were all checked and are 
summarized in the following table : 



Solution of Adrenalin Chloride. 



Solution of Synthetic Sub- 



First Method : 

Cotton plugged > 

tube in boiling j 

water 15 minutes j 

at a time. J 

Second Method : 
Tightly stop- 
pered bottle 
in boiling water [ 
15 minutes at a time. J 

Third Method : 
Boiled 5 
minutes over 
flame in open 
flask. 



1st ster. 
per 



1. IOO 

2. IOO 



1. IOO 

2. IOO 



1. IOO 

2. IOO 



2nd. 
per 



IOO 
IOO 



IOO 
IOO 



IOO 
IOO 



3rd. 
per 



4th. 
per 



1st ster. 
per 



stance. 
2nd. 
per 



cent. cent. 



3rd. 4th. 
per per 
cent. cent. 



90 
90 



IOO 

90 



90 
IOO 



80 
90 



90 
90 



75 
90 



1. 100 100 80 80 



1. IOO 

2. IOO 



1. IOO 

2. IOO 



IOO 
90 



90 
90 



70 
80 



80 
80 



70 



75 
80 



The results obtained show that Adrenalin Chloride Solution 1 in 
1000, containing no preservative other than a slight excess of hydro- 
chloric acid, can be sterilized at least twice by heating to the tem- 
perature of boiling water under various conditions without losing 
any activity. After this the loss is quite gradual, so that it prob- 
ably would not be noticeable therapeutically until after the fourth 
or fifth sterilization. By a comparison of the results obtained -with 
Adrenalin Chloride Solution and the solution of the synthetic sub- 
stance it can be seen that the loss of activity due to sterilization 
occurs more quickly in the case of the latter solution and also that 
the deterioration is more marked. 



Summary. 

1. Adrenalin Chloride Solution in ampoules can be heated con- 
tinuously for 3 hours to the temperature of boiling water without 
any loss of activity. 

2. Adrenalin Chloride Solution in ampoules can be sterilized by 
immersion in boiling water for seven distinct periods of 15 minutes 
each without loss of activity. 



Am Ap?n r 'i9i h 4 rm " } Solubility of Phenol in Hydrocarbons. 149 

3. Adrenalin Chloride Solution can be exposed to the air and 
sterilized at least twice under a variety of conditions without loss 
of activity. 

4. Adrenalin Chloride Solution is more stable than the Solution 
of a synthetic compound when both are subjected to the same sterili- 
zation treatment. The results obtained disprove the statement that 
the stability of the synthetic exceeds that of the natural product. 

REFERENCES. 

1 Aldrich : Jour. Amer. Chem. Soc, September, 1905. 

2 Stoll : Lancet-Clinic, June 21, 1913. 

3 Houghton: Jour. Amer. Med. Assoc., January 18, 1902. 

From the Research Laboratory of Parke, Davis & Co., Detroit, 
Michigan. 

NOTE ON THE SOLUBILITY OF PHENOL IN 
HYDROCARBONS. 

By J. D. PlLCHER. 

Pharmacological Laboratory, School of Medicine, Western Reserve 
University, Cleveland. 

The Pharmacopoeia states that Phenol is very soluble in fixed 
oils. It is less soluble in the mineral oils ; as determined in this 
laboratory one gram of Phenol dissolves in 8-9 c.c. of Petroleum, 
20-21 c.c. Petroleum benzine, 45-50 c.c. of Petrolatum liquidum. 
It is about twice as soluble in solid Petrolatum (1 in 23-24) as in 
the liquid petrolatum. This difference in solubility of Phenol in 
the vegetable and animal oils and in the mineral oils is worthy of 
note for two reasons : In removing Phenol from the skin after acci- 
dental application the mineral oils would be less efficacious than the 
fixed oils, glycerin and alcohol and of little more value than water. 
However, when the local "action is desired, ointments and liquid 
preparations of Phenol in the mineral oils would be more active than 
preparations containing the same percentage of Phenol in the animal 
or vegetable oils, inasmuch as the mineral oils would part with the 
Phenol more readily than the other oils. 

Methods. — Weighed amounts of crystallized Phenol were added 
to the liquid hydrocarbons and allowed to stand, with frequent 



Paraffin Oil. 



(Am. Jour. Pharra. 
t April, 1914. 



shaking, several hours or over night. Small quantities of the oils 
were then added until the Phenol was completely dissolved. In dis- 
solving the Phenol in the petrolatum the mixture was thoroughly 
stirred while heating to the melting point; on cooling, the mixture 
was examined microscopically for Phenol crystals and, when found, 
the process was repeated with the addition of small amounts of 
petrolatum until no crystals were visible. 



RENEWED INTEREST IN PARAFFIN OIL. 1 
By M. I. Wilbert, Washington, D. C. 

Within recent years renewed interest is being taken in paraffin 
oil for internal administration in the treatment of intestinal stasis 
or chronic constipation. This renewed interest is largely due to the 
fact that a notable English surgeon, Sir W. Arbuthnot Lane, in his 
experimental work to prevent the formation of adhesions after sur- 
gical interference in the intestinal tract, found that paraffin oil 
served as an intestinal lubricant and was of material assistance in 
overcoming persistent constipation. 

This use of paraffin oil is by no means" new, however, and-dates 
back many years to the introduction of refined petroleum products 
by Cheseb rough and others about 1872. 

Previous to this date the residues in petroleum stills had little 
or no commercial value and were used almost exclusively as lubri- 
cants, more particularly axle grease. The possibility of producing 
an odorless and practically colorless oil and heavier fat by compara- 
tively simple methods, presented the peculiar problem of establishing 
a market for products of this kind and for some years at least the 
substances were used largely, if not exclusively, for the adulteration 
of other fats and oils, and it is this use of vaseline and of vaseline 
oil as adulterants that later led to experiments to demonstrate their 
possible food value and the presence or absence of harmful or toxic 
ingredients. Experiments carried on by N. A. Randolph, Philadel- 
phia, about 1884, not only demonstrated that the heavier petroleum 
products were not absorbed from the intestinal tract but also showed 
that they served to act somewhat in the nature of foreign material, 

1 Presented at the meeting of the City of Washington Branch of the A. 
Ph. A., March 18, 1914. 



Am. Jour. Pharm. ) 
April, 1914. / 



Paraffin Oil. 



and might have some value in the treatment of certain forms of con- 
stipation. It was also thought that these products appeared to inhibit 
fermentation and would, therefore, be of value in the treatment 
of certain forms of diarrhoea. Some fifteen years later, Robert 
Hutchinson of England reported practically the same observations 
and this report led to the then quite extensive use of petroleum 
and of paraffin oils for various intestinal disorders. 

The at one time widespread use of purified petroleum products 
in the treatment of pulmonary disorders, is, to some extent, traceable 
to the administration of the naturally occurring petroleum products 
in various countries and at various times. Crude petroleum has been 
used from time immemorial as a medicine and perhaps largely be- 
cause of its disagreeable odor was from very early times used in 
the treatment of diseases of the respiratory tract. In this country 
" Seneca oil " had considerable vogue from time to time and was 
frequently put out in the form of proprietary or " patent prepara- 
tions " for the treatment of various diseases. After the introduction 
of purified petroleum products these were offered as substitutes for 
the formerly used crude oil and, even at the present time, the adver- 
tising matter put out in connection with some of the popularly ex- 
ploited preparations of petroleum do not satisfactorily designate 
whether or no the crude or the purified product is being advocated. 

During the past three or four decades, purified petroleum products 
have been marketed under scores, if not hundreds, of proprietary 
names and the misleading claims and statements made in connection 
with these several preparations are far from being a credit to the 
owners or to the persons who act as distributers for the several 
articles. That there is some element of truth in the claims that have 
been made for petroleum products is evidenced by the fact that the 
use of petroleum, crude and refined, has persisted in all parts of the 
world and has at times, like the present, reached amounts that were 
quite considerable. 

With the renewed interest in paraffin oil that is in evidence at 
present, the time appears to be particularly opportune for pharma- 
cists who are willing to assist in making for true progress to do 
missionary work and to point out to physicians in a rational and 
sensible way that paraffin oil and other petroleum products, while 
they may be useful, must have limitations, that many of the claims 
made for the proprietary articles are unfounded and not based on 
fact, that in the event that the physician does wish to experiment 



Paraffin Oil. 



f Am. Jour. Pharm. 
\ April, 1914. 



with the product, non-proprietary oils of high quality are readily 
available and, finally, that these non-proprietary products can be 
sold to the patient at a very much lower figure than can the pro- 
prietary article and still yield the retail druggist a more satisfactory 
profit. 

As intimated above, the products that are available at the present 
time are many, or at least appear to be numerous because of the 
varied trade names under which they are offered. On studying the 
nature of these products, however, it appears that there is no very 
great difficulty in establishing certain, at times perhaps arbitrary, 
lines of demarcation between them and identifying them as belong- 
ing to one or the other class of commercially available oils readily 
obtainable by any pharmacist. 

The bulk of the available supply of heavy mineral oil comes from 
two sources and the products differ materially in chemical composi- 
tion. The American oil is obtained from paraffin base petroleum and 
consists essentially of hydrocarbons of the methane series having the 
general formula CnH 2 n -f- 2 . 

The so-called Russian Oil, obtained largely, if not entirely, from 
the oil wells in the Baku district, consists chiefly of monocylic poly- 
methylenes or napthenes, having the general formula CnH 2 n. 
These latter products have been described as hydrated aromatic 
hydrocarbons and while they behave with reagents very much in the 
same way as do the hydrocarbons of the methane series, they are 
more readily purified and generally occur in commerce as water 
white oils that are quite free from fluorescence or odor. The Amer- 
ican paraffin or methane oils usually have a distinct color and are 
seldom quite free from fluorescence or a peculiar dichroic effect 
that is particularly noticeable when the preparation is viewed by 
reflected light. Apart from the appearance, however, there is no 
evidence that the two products differ in their effect on the animal 
organism and one has perhaps as many advocates and users as the 
other. 

The density of the commercially available products also varies 
and the fact that it is proposed to extend the present U. S. P. limits 
of specific gravity, 0.870 to 0.940 at 25 °, to read 0.845 to 0.940 at 
25 clearly indicates that the members of the present Committee of 
Revision are themselves not convinced as to the properties that 
should be inherent in a mineral oil for medicinal use. 

The paraffin oils official in the Pharmacopoeias of the Continent 



Am. Jour. Pharm. > 
April, 1914. } 



Paraffin Oil. 



153 



of Europe are usually of the denser variety, 0.865 or higher at 15 , 
but this is probably due to the fact that there the oil is largely used 
as a basis for ointments and the various other uses are only now 
being developed. 

In this country paraffin oil or$ as it is better known, liquid petro- 
leum, has long been in use as a basis for oil sprays in the treatment 
of affections of the nose and throat and for this purpose the lighter 
and more limpid oil appears to be preferred. For internal adminis- 
tration Sir W. Arbuthnot Lane prefers the heavier, European type 
of oil and this is now available in this country and is being intro- 
duced by a number of manufacturers and dealers under proprietary 
titles, to be sold at fancy prices. Even for internal use, however, 
there appears to be a definite limit to the solid paraffin that an oil 
can hold in solution and be palatable or readily taken. At compara- 
tively low temperatures some of these oils are nearly solid and even 
at ordinary temperatures they are so viscid that they do not readily 
leave the mouth when taken internally. 

Up to the present time it is by no means positively established 
that the comparatively dense or the viscid oil is to be uniformly pre- 
ferred for internal administration, and the pharmacist can be of 
service not alone in assisting the physician to determine which of 
the two products is the preferable one but also in devising methods 
of administration and preferable flavors to overcome the objection- 
able taste of the oil, particularly of the denser variety of oil. 

One further question that may be discussed briefly is the dose. 
One firm, the owner of the product most widely used in this coun- 
try, says : 

" Excellent results are obtained by giving the oil in small doses. 
In mild cases a tablespoonful at night gives prompt relief. In longer 
standing cases make it almost a part of the diet and give one or two 
teaspoonfuls just after meals." 

Dr. Lane and many of his followers, on the other hand, give the 
oil in much larger doses and insist that it be given shortly before 
meals so as not to interfere in any way with the digestion of food 
which it probably would if, as proposed above, it were given with or 
immediately after meals and thereby intimately mixed with the 
stomach content. 

Bastedo, in his book on materia medica, pharmacology, thera- 
peutics and prescription writing, states that the oil is only mildly 
laxative and should be given in doses of 30 c.c. two or three times 



154 



Paraffin Oil. 



Am. Jour. Pharm. 
April, 1914. 



a day. Other authorities advise even larger doses, and Robinson 
(Medical News, 1900, v. 77, p. 56) reports that he frequently admin- 
istered nearly a pint in a few hours without any indications of dis- 
comfort and no untoward results of any kind. Robinson also asserts 
that he was able to duplicate the experiments reported by Randolph 
and reclaim all of the oil that was ingested. Some recent German 
experimenters, however, appear to believe that a part, at least, of 
the oil is changed or absorbed in the intestinal tract, and while the 
bulk of it passes through unchanged it is not possible to reclaim 
absolutely all of the oil as taken. At the present time, the preferred 
dose is from one to two tablespoonfuls one hour before meals, 
or from two to four tablespoonfuls on retiring. The oil may be 
flavored to make it less objectionable, and several authorities appear 
to prefer administering the product in the form of an emulsion, 
though others claim that the emulsion is not so satisfactory and 
does not give the same uniform good results. 

In addition to its use internally as a lubricant or laxative, paraffin 
oil is also given in the form of rectal injections, and is being ex- 
ploited more recently as a dressing for wounds, both recent and 
chronic. In connection with chronic ulcers it is being extolled as a 
dressing to protect the skin around the focus of suppuration. The 
oil in these cases not alone protects the skin against irritation from 
oozing, thus warding off eczema, but also keeps the dressings from 
sticking. 

The use of liquid petroleum as a soothing application in the form 
of a spray to inflamed mucous membranes of the. nose and throat 
is well-known, as is the use of the same product in cosmetics, such 
as skin creams or pomades, and the use of this product for these 
several purposes need not be discussed at this time. 

In conclusion, then, the object of this communication is to call 
attention to the renewed interest that is being manifested by medical 
men in paraffin oil for internal administration, and as an adjuvant 
dressing for wounds, and to suggest to pharmacists that they ac- 
quaint themselves with the properties of the available material for 
the purpose of pointing out to physicians the nature and the kind of 
material that is available as well as the limitations that probably 
exist. 



^ m Ap°r?Ci9H rm '} United States Public Health Service. 155 



THE UNITED STATES PUBLIC HEALTH SERVICE. 1 



By John F. Anderson, Director Hygienic Laboratory, U. S. Public Health 
Service, Washington, D. C. 

The Federal Public Health Service is a bureau of the Treasury 
Department. Beginning- as the Marine Hospital Service, through 
successive acts of Congress it has undergone a process of evolution 
so that all of its duties are essentially of a public health character, 
and it is organized with a view to their performance. 

The central bureau at Washington, which is presided over by 
the surgeon-general, has seven divisions, as follows : 

1. Personnel and accounts. 

2. Foreign and insular quarantine and immigration. 

3. Domestic (interstate) quarantine and sanitation. 

4. Sanitary reports and statistics. 

5. Scientific research. 

6. Marine hospitals and relief. 

7. Miscellaneous. 

Each of the six divisions first mentioned is in charge of an 
assistant surgeon-general, who is directly responsible for administra- 
tive matters in connection with his division. The officer who' has 
charge of the Division of Personnel and Accounts has immediate 
supervision of the entire personnel and appropriations, and the 
preparation of the annual estimates therefor. 

Through the Division of Foreign and Insular Quarantine and 
Immigration are administered all matters relating to maritime quar- 
antine and medical inspections of aliens. 

Through the Division of Interstate Quarantine are administered 
all matters relating to the control of contagious and infectious dis- 
eases in interstate traffic. 

The Division of Sanitary Reports and Statistics handles all 
matters relating to the collection of morbidity reports, reports of 
epidemics, and of information pertaining to the geographic distri- 
bution of disease and to climate in relation to> health and disease. 

The Division of Scientific Research administers all matters re- 
lating to* investigations of contagious and infectious diseases and 

1 Abstract of a lecture delivered by invitation March 9, 1914, before the 
Philadelphia College of Pharmacy. 



156 United States Public Health Service. { Am • A ^• 1 p ^Jf^• 

matters pertaining to the public health wherever made. In the field 
it is represented by the Hygienic Laboratory with its four divisions, 
the plague laboratory in San Francisco, the leprosy investigation 
station in Hawaii, the pellagra investigation station at Savannah, 
Ga., the station at Wilmington, N. C, for the investigation of the 
parasites of man, and by officers engaged in investigations of typhoid 
fever, Rocky Mountain spotted fever, poliomyelitis, etc., in dif- 
ferent parts of the country, and sanitary surveys of navigable waters 
wherever conducted. 

In the Division of Marine Hospitals and Relief are administered 
all matters connected with the care and treatment of seamen and 
recruiting for the several bureaus of the department. 

To-day the Public Health Service has a corps of approximately 
450 medical officers, 50 pharmacists, and a total personnel of 
about 2,000. 

In the public health law of July 1, 1902, provision is made for 
annual conferences between the Public Health Sendee and state 
boards and departments of health. Provision is also made for special 
conferences with all or a part of the state health organizations, and 
upon the application of not less than five state health authorities, a 
special conference must be called. In effect, there is thus provided 
an advisory council on administrative matters, which in its devel- 
opment will insure cooperation and be an arbiter on vexed sanitary 
questions, and in which each state is entitled to representation. 

In the same law Congress also provided for an advisory board 
for consultation relative to investigations to be inaugurated and 
the methods of making them in the Hygienic Laboratory. By this 
means the service is brought in touch with the great scientific labora- 
tories, and may avail itself of advice from the highest sources. 

Congress has thus made provision for councils in respect to both 
administrative and scientific matters. Their utilization in the highest 
degree is one of the most important means of development of public- 
health organization and public-health work. 

The necessity for more ana 1 more extensive Federal supervision 
over international traffic was made apparent by repeated epidemics. 
The first permanent quarantine law, passed April 29, 1878, was a 
result of the widespread and severe epidemic of yellow fever during 
the previous year. The passage of the law of February 15, 1893, 
was intimately associated with the outbreak of cholera in Europe in 
1892, and the quarantine act of June 19, 1906, followed the epidemic 



m 'Av£*; ml™'} United States Public Health Service. 157 

of yellow fever in the Southern States in 1905. Under the above- 
mentioned laws and a few minor ones, there was finally developed 
the national system of quarantine as it exists to-day — a system, the 
development of which occupied approximately 100 years. 

All quarantine operations in the United States are conducted 
under the supervision of the Federal Government, and, with two or 
three exceptions, all stations are conducted by Federal officers. 

A long series of immigration laws have been enacted between 
the periods March 20, 1819, and February 20, 1907, their general 
objects from a hygienic standpoint being the improvement of the 
health and comfort of arriving aliens, and the development of a 
stronger race in the United States. 

On arrival at domestic ports, all aliens are required to undergo 
medical inspection, and for those suffering with disease, hospitals 
are maintained. This medical inspection is conducted by the Public 
Health Service. 

The administrative procedures in international sanitation having 
been established, and their further improvement assured, the great 
public health problems of the Nation are now of an interstate and 
intrastate character. 

The Federal public health statutes are based upon, or are care- 
fully in accord with that clause of the Constitution which gives the 
right to Congress to regulate commerce between the states. On 
account of the far-reaching effect of interstate intercourse on our 
national life, the field for public health activities on the part of the 
Federal Government is wide. 

Under the quarantine act of February 15, 1893, the secretary of 
the Treasury is authorized to issue regulations for the prevention 
of the spread of infectious and contagious diseases from one state 
to another, where the regulations of the states are inadequate. 
These regulations may be enforced by state and local authorities, 
but the Federal Public Health Service is authorized to cooperate in 
their enforcement, and should the states fail or refuse, the Presi- 
dent may adopt such measures as in his judgment shall be necessary. 

Examples of work of this character that may be mentioned are 
cooperative measures for the collection and examination of rodents 
to prevent plague; anti-typhoid campaigns in urban and rural dis- 
tricts, and sanitary surveys of interstate and international waters in 
relation to the prevention of the spread of typhoid fever. 

There is necessity not only of quarantine measures to prevent the 



158 United States Public Health Service. | Am ipSi r 'i34 ™* 

spread of communicable diseases, but sanitary measures to prevent 
their propagation. These include the sanitation of trains and vessels 
and the supplies used aboard, the regulation of conditions under 
which the employees of common carriers work, and the exclusion of 
dangerous or infected merchandise from transportation. 

On account of the relation of epidemics to the hygienic and 
commercial welfare of the country, the Federal Public Health Service 
may, under the provisions of the above-mentioned law, assume re- 
sponsibilities in respect to their control under the direction of the 
Secretary of the Treasury and the President. In the event of out- 
breaks of cholera, yellow fever, smallpox, plague, or typhus fever 
in any part of the United States, the President is also authorized to 
cause regulations to be issued and enforced to prevent their spread, 
and an epidemic fund of approximately half a million dollars is 
appropriated annually for expenditures of the Federal Public Health 
Service in suppressing epidemics of these diseases. 

It is under such authority that the epidemics of yellow fever in 
the Southern States, the outbreaks of plague in California and our 
island possessions, and similar outbreaks have been handled. 

Relation of the Public Health Service to Pharmacy, 

The reorganization of the Marine-Hospital Service in 1871, under 
the direction of a supervising surgeon-general, materially broadened 
the object and scope of the service and evidenced the advisability of 
extending the work so as to provide for much needed supervision 
of varied interests relating to the public health. 

Of the many activities that were early developed by the service 
in this connection, few are of more wide-spread importance to the 
welfare of the public at large, or more intimately connected with 
the medical efficiency of the service itself, than the efficient control 
of medicinal substances and active participation and interest in the 
revision of the Pharmacopoeia of the United States. This service 
has been regularly represented at each decennial meeting of the 
Pharmacopceial Revision Convention held since its reorganization 
as a bureau in 1871, and several of the representatives of the Marine- 
Hospital Service have served as members of the revision committee. 
The first of the representatives of the service to be elected to serve 
as a member of the Committee of Revision was a pharmacist, Oscar 
Oldberg, who was the delegate of the then U. S. Marine-Hospital 



***a.^ST" iSSC™" } United States Public Health Service. 159 

Service to the Pharmacopceial Convention in 1880. This service was 
also among the first of the government services to adopt the phar- 
macopoeia as the standard for its medical supplies and to require 
that drugs and medicines conform strictly with these official require- 
ments. 

In this connection it may also* be of interest to point out that 
this service was the first to systematically use the metric system of 
weights and measures and that this use of the metric system by one 
of the government medical services played a very important part in 
the practical adoption of the metric system of weights and measures 
in the sixth decennial revision of the Pharmacopoeia of the United 
States. 

The use of the metric system of weights and measures was made 
compulsory in the then " Marine-Hospital Service " by an order 
signed by the Secretary of the Treasury, John Sherman, in 1878, at 
the request of Prof. Oldberg, and the steps that led up to the sign- 
ing of the order are well foreshadowed in the report of the Super- 
vising General, John M. Woodworth, on the operation of the Marine- 
Hospital Service for the fiscal year 1877, which includes a lengthy 
report on the adoption of metric system of weights and measures 
for medical and pharmacal purposes, by Oscar Oldberg, then chief 
clerk and acting medical purveyor of the United States Marine- 
Hospital Service. 

With the change of name to the Public Health Service, the need 
for cooperation in improving the available supply of remedies used 
in the treatment of diseases and the perfecting of the scientific accu- 
racy in pharmacopceial requirements has become more and more ap- 
preciated and provisions have from time to time been made for active 
cooperation in the work of associations interested in the promulga- 
tion of the truth regarding the nature of medicines of various kinds. 
The general importance of this work from a public health point of 
view had in a measure been foreseen by the inauguration of the 
Division of Scientific Research and the establishment in the Hygienic 
Laboratory of a division of pharmacology devoted to the scientific 
investigation of drugs as they relate to the public health, particu- 
larly as to their potency, efficiency and pharmacopceial purity. Also 
and in a more direct way, by the authorization by law to undertake 
the supervision and practical control of certain important medicinal 
products, such as sera and vaccines. 

In 1902 Congress passed a law requiring that all persons or firms 



160 United States Public Health Service. { Am XprS r 'i9i4 arm * 

engaged in the manufacture and interstate sale of viruses, serums, 
toxins, and similar products should be licensed by the Secretary of 
the Treasury for the sale of such products. An inspection has to be 
made of the stables, methods, etc., of the firm desiring to be licensed 
and an examination of all their products has to be made in the 
Hygienic Laboratory. After a consideration of the inspector's re- 
port on the firm's plant and the report on the examination in the 
Hygienic Laboratory of the various products, a license is either 
issued or declined. In connection with the enforcement of this 
law the Public Health Service has promulgated certain regulations 
to govern those engaged in the manufacture of these important ther- 
apeutic products and has established standards for the measurement 
of the potency of some of them. 

For a number of years members of the staff of the Hygienic 
Laboratory have actively cooperated in the work of the Council on 
Pharmacy and Chemistry of the American Medical Association, the 
Committee on National Formulary of the American Pharmaceutical 
Association and the Committee on Non-official Standards of that 
latter Association. 

This cooperative work done by members of the staff of the 
division of pharmacology in connection with these several commit- 
tees is no doubt familiar to you and need not be specifically reviewed 
at this time. 

The division of pharmacology of the Hygienic Laboratory has 
also contributed much in the way of cooperative work on the revision 
of the pharmacopoeia and has undertaken the study of a number of 
problems in connection with the present revision. The results have 
from time to time been published either in the form of bulletins or 
in papers contributed to the pharmaceutical or medical journals. 
Up to date these studies include: The standardization of thyroid 
products; the standardization of the adrenal gland products, more 
particularly; the standardization of epinephrine; the physiological 
standardization of the official preparations of digitalis and ^f ergot; 
the possible standardization of tincture of caramel, and comprehen- 
sive investigations on the solubility and on the melting point of 
official chemical substances. 

Of even more direct interest to pharmacists as an illustration of 
the nature of cooperative work done in the Hygienic Laboratory are 
the publications of the series of " Digest of comments on the Phar- 
macopoeia of the United States and the National Formulary." 



Am ApS"'i9i4. rm '} United States Public Health Service. 161 

This work of abstracting the literature relating to the Pharma- 
copoeia of the United States and the National Formulary was under- 
taken at the request of the board of trustees of the United States 
Pharmacopoeial Convention, with the sanction of the Secretary of 
the Treasury, and the compilations have appeared in the form of 
bulletins covering the literature of the calendar years from 1905 to 
date. This work has received high commendation from physicians, 
pharmacists and chemists in all parts of the world. The eminent 
pharmacognosist, A. Tschirch, in commenting on this work, admits 
that practical Americans were the first to recognize the importance 
of conserving intellectual energy in connection with the revision of 
the pharmacopoeia and comments favorably on the comprehensive- 
ness of the " Digest of Comments." Pharmaceutical and medical 
journals generally have commented favorably on the several bulletins 
and have uniformly voiced the opinion that these bulletins represent 
a work of great utility and because of the fact that they bring to- 
gether with remarkable clearness the public comments on pharma- 
cology and materia medica and thus form an index of the work of 
the year such as is not published elsewhere. 

In addition to the work done in connection with the pharma- 
copoeial revision and the standardization of drugs and preparations, 
there has also been published as Public Health Bulletin No. 56 a 
" Digest of the Laws and Regulations in Force in the United States 
Relating to the Possession, Use, Sale, and Manufacture of Poisons 
and Habit-Forming Drugs." This is the first complete analytical 
compilation of the laws on this subject, and provisions have been 
made to keep the material up to date by the publication of new 
legislation in Public Health Reports and the reprinting of this mate- 
rial from time to time as separates. The first of these reprints, 
covering the legislation enacted during 1912 and 1913, is now being 
distributed. 

As an illustration of the relative importance of matters phar- 
maceutical to public health work, it may be pointed out that of the 
90 bulletins published by the Hygienic Laboratory, no less than 39 
are of direct interest to the pharmacist, or have some distinct bear- 
ing on the practice of pharmacy. In addition to the 7 volumes on 
the " Digest of Comments," this list includes the very popular bul- 
letin of 122 pages on the Changes in the Pharmacopoeia of the 
United States of America, eighth decennial revision, compiled by 
Doctors Reid Hunt and Murray Gait Motter, published in 1905. 



1 62 United States Public Health Service. \ Am jour pnarm. 

\ April, 1914.^ 

Six bulletins deal specifically with the physiological standardization 
of drugs, four deal with the chemical or physical standardization of 
official substances, nine discuss the use and standardization of anti- 
septics, disinfectants and germicides, six refer more specifically 
to sera and vaccines, and six involve comprehensive studies of 
chemical tests and other problems of interest to pharmacy. 

In addition to the work done in the Hygienic Laboratory prac- 
tical observations of interest to pharmacists are from time to time 
reported by individual pharmacists attached to the several stations 
in different parts of the country. 

The present corps of pharmacists includes 16 pharmacists of 
the first class, 24 pharmacists of the second class, and 6 pharmacists 
of the third class. 

Sanitary reports and statistics and the results of scientific inves- 
tigations are of value only as they are made public and used. Among 
the publications issued by the Service are the Hygienic Laboratory 
bulletins, bulletins of the Yellow Fever Institute, Public Health bul- 
letins, the weekly public health reports, and miscellaneous docu- 
ments. The Hygienic Laboratory bulletins represent the results of 
scientific investigations conducted in the laboratory. The public 
health bulletins are popular in character, and are utilized to convey 
sanitary information to health officials and to the public generally. 
The weekly public health reports are issued primarily for the benefit 
of health authorities as an aid in administration. 

Another important function of the Public Health Service in 
relation to the public health, and perhaps the most important one, is 
the conduct of scientific investigations. 

By an act of March 3, 1901, investigations of contagious and 
infectious diseases and matters pertaining to the public health were 
given definite status in law. Provision was made whereby laboratory 
investigations would be systematically carried on. Through this 
provision and in connection with the enforcement of the quarantine 
laws investigations have been made in Washington and different 
parts of the country. In order to comply with the law, however, this 
work was carried on largely through the Hygienic Laboratory. 

By an act of Congress approved August 14, 1912, broader powers 
were conferred on the Public Health Service to " study and inves- 
tigate the diseases of man and conditions influencing the propagation 
and spread thereof, including sanitation and sewage and the pollu- 



Am. Jour. Pharm. 1 
April, 1914. j 



Lecithin. 



tion, either directly or indirectly, of the navigable streams and lakes 
of the United States." 

There is thus abundant authority for both laboratory and field 
investigations by the Public Health Service. As in the past the 
investigations will be conducted by officers specially trained and with 
such cooperation as state and local health authorities may be able 
to render. But in order that the great needs of the country may 
be met, more men and more money must be provided and the Public 
Health Service must have the active support of individuals, profes- 
sional associations, and other organizations to be benefited. 

Many highly important problems await solution. Among them 
may be mentioned the standardization of biologic and other thera- 
peutic products, the determination of the conditions causing pellagra 
and certain other diseases, the extent of the migrations of tubercu- 
lous and other patients from one locality to another, the ascertain- 
ment of the influence of artificial illuminants on health, the determi- 
nation of the relation of housing and other conditions to labor 
efficiency, and the prescribing of reasonable standards to control 
stream pollution. 

Requests are received daily from all parts of the country for in- 
formation regarding sanitary problems and methods of handling 
them. These requests are an excellent indication of the amount and 
extent of work to be performed in the immediate future. In one 
section of the country the question of the pollution of streams is 
pressing for solution ; in another, it may be industrial accidents and 
poisoning; in another, the question of the reduction of infant mor- 
bidity; and in still another, the measures that must be taken to 
eradicate malaria and other communicable disease. 



LECITHIN.* 

In the economy oi living cells belonging to the vegetable and 
animal kingdoms, a very important part is played by a certain group 
of bodies, which are generally spoken of collectively as " lipoids." 1 

* Reprinted from E. Merck's Annual Report, 1912, vol. xxvi., pp. 1-22. 

1 The word " lipoid " is derived from the Greek "kt%oq — fat. It denotes 
fatty substances which contain phosphorus, or phosphorus and nitrogen, or 
neither of these elements, and which have special functions to perform in the 
cell. An exact definition of the term " lipoid " cannot be given. Kletzinsky 



164 



Lecithin. 



( Am. Jour. Pharm. 
X April, 1914. 



Among the best known members of this group are the cholesterins 
and lecithins. While the cholesterins are organic combinations free 
from nitrogen and phosphorus, the lecithins contain both nitrogen 
and phosphorus. They are grouped together as a special class of 
bodies, the so-called " phosphatides," 2 comprising a large number 
of representatives. The phosphatides are characterized by contain- 
ing one or more molecules of phosphoric acid, an alcohol (for ex- 
ample glycerin), one or more fatty acid radicles (for example 
stearic or oleic acid) and one or more nitrogenous bodies (such as 
choline and allied substances). Lecithin, or rather the lecithins, are 
phosphatides of this description. The theoretical formula of the 
lecithins is as follows: 



It is highly probable that other substances containing nitrogen and 
allied to choline may occur in natural lecithin, but so far choline alone 
has been demonstrated with certainty in the decomposition products 
of the lecithins. The radicles of stearic, palmitic and oleic acid (R in 
the above formula) are present in the form of esters with the glyc- 
erin radicle in the lecithin molecule. It has not yet been possible 
to determine whether one molecule always contains either two similar 
or two different acid radicles. Although in the examination of 



understood it to mean those substances which cannot be saponified and which 
may be extracted from animal cells by means of alcohol and ether. If their 
non-saponification be left out of account, for it applies to cholesterin but not 
to lecithin, the designation " lipoid " may still be defined in the terms of the 
author mentioned above, for Overton considers it to denote all those com- 
ponents of the cell which, like fat, will dissolve in ether, chloroform and 
similar organic liquids. Kraus termed lipoids " noble fats " to distinguish 
them from fats. 

2 Lecithin is a mono-amino-mono-phosphatide, which denotes that still 
more complex substances exist, e.g., di-amino-mono-phosphatides, mono- 
amino-di-phosphatides, di-amino-di-phosphatides, tri-amino-mono-phospha- 
tides, etc. These bodies have not as yet been exhaustively investigated. (Com- 
pare Thudichum.) 

It should be noted that at the end of the original article in Merck's 
Report a detailed list of the literature is given, arranged according to authors. 



/O.R 
C 3 H 6 ^-0 . R 




OH-$P=0 



/C 2 H 4 -0 
NHCH 3 ) 3 
\OH 



Am. Jour. Pharm. \ 
April, 1914. j 



Lecithin. 



165 



lecithin obtained from egg yolks stearic acid and palmitic acid or 
oleic acid are usually found, this is not a proof that these acids are 
derived from a single molecule ; for a mixture of stearyl and 
palmityl-lecithin, or of stearyl and oleic acid-lecithin may equally 
well be present. But in the text-books of physiology or of physio- 
logical chemistry, lecithin from egg yolks is occasionally represented 
by the assumptive formula of stearyl-palmityl-lecithin : 



The structure of this formula may most probably be traced back to 
the statements of Thudichum ; in his opinion a lecithin molecule 
always contains one saturated and one unsaturated fatty acid resi- 
due. According to him, every true lecithin contains at least one 
fatty acid radicle and always represents a mono-amino-mono-phos- 
phatide, — e.g., the molecule contains only one atom of nitrogen and 
one atom of phosphorus. 

It is generally assumed that the lecithin from egg yolks is mainly 
stearyl-lecithin and the lecithin obtained from plants mainly oleic 
acid-lecithin. In how far this assumption is supported by facts 
cannot be decided on the strength of the researches on the lecithins 
so far carried out. It is indeed doubtful whether the above formula 
definitely explains the constitution of the natural lecithins. 3 The 
investigations of MacLean, Otolski, Cousin, Erlandsen, Henriques 
and Hansen have shown that the lecithins, besides containing cho- 
line, also possibly contain other nitrogenous disintegration products 
(pyridine) and other unsaturated fatty acids (linoleic acid and lino- 
lenic acid). This may also be inferred from the relatively high 
iodine number of the lecithins, which is not sufficiently explained 
by their content of oleic acid. Nor can it be decided whether cal- 
cium and iron, which always accompany the lecithins, form an 
essential part of the lecithin molecule or are merely impurities ; thus 
no great weight can be attached to the constitutional formula of 
lecithin. Further, Malengreau and Prigent, as a result of hydro- 

8 According to Thierfelder and Stern, other phosphatides besides lecithin 
occur in egg yolks. These have also been found by Thudichum, Hammarsten, 
Erlandsen and others in various animal organs. 



/ O . CxsHwO 
C3H5— O . CigHsiO 




OH— P=0 



/C 2 H 4 — O 
N=(CH 3 ) 3 



Lecithin. 



(Am. Jour. Pharm. 
\ April, 1914. 



lytic experiments, have expressed doubt as to the possibility of an 
ester-like combination between choline and phosphoric acid. It is 
certainly true that the natural lecithins, however carefully they are 
purified, always represent mixtures of various lecithins. The 
physical condition of pure commercial lecithin, which is waxy and 
occasionally somewhat crystalline, is in favour of this view ; and it is 
justifiable to assume, according to the present position of research 
on lecithin, that the separate lecithins which constitute natural 
lecithin, in their absolute chemical individuality and purity, are 
crystalline bodies. 

The solution of this problem is, however, of more chemical than 
physiological or therapeutic interest. As is evident from an inves- 
tigation by Stepp, those lecithins alone are of physiological or thera- 
peutic importance which are produced by the living organism itself 
for its own use. It is therefore probably justifiable in therapeutics 
to speak of pure lecithin when this consists solely of lecithins with- 
out admixture of albumins or of lecithalbumins. My Lecithinum*ex 
ovo purissimum is a preparation of this nature. 

The discovery of lecithin is usually attributed to Gobley (1846), 
although long before him Vauquelin (1811) and Couerbe (1834) 
found and described phosphorus-containing fats in the brain, which 
were probably identical with lecithin. Fremy, a pupil of Couerbe, 
named Vauquelin's substance " oleo-phosphoric acid," as he found 
its products of decomposition to consist of glycerin, phosphoric 
acid and oleic acid. In conjunction with Valencienne he isolated the 
same substance from the roe of fish. But Gobley was the first to 
prepare it from the yolk of eggs, and he called it " matiere vis- 
queuse," and later, on account of its origin, " lecithin," from 
Aex-i&og (=yolk of egg). 4 He was also the first to recognise the 
principal component of lecithin possessing physiological importance, 
namely glycerophosphoric acid, which is obtained by the careful 
saponification of lecithin; he thus established the basis for the con- 
stitution of the lecithin molecule which is still fairly generally 
accepted. The basic component of lecithin, choline, was discovered 
by Liebreich and Strecker. 

Lecithin is therefore regarded as a glycerophosphoric acid in 



* Strecker's view (Annalen der Chemie und Pharmazie, 1868, Vol. 72, p. 
77) that the word lecithin is derived from floe (= oil jar) and should 
therefore be written lecythin, is erroneous. 



Am. Jour. Pharm. \ 
April, 1914. J 



Lecithin. 



.OH 
C 3 H 5 ^OH 

\CK Glycerophosphoric acid. 

OH^P=0 
OH/ 

which the hydrogen atoms of the hydroxyls of glycerin are replaced 
by fatty acid radicles, and one hydrogen of the phosphoric acid 
residue by a choline radicle. Theoretical consideration shows that 
two possible formulas exist, one symmetrical and one asymmetrical, 
according to the position of the fatty acid residues in the glycerin, 
thus : 

/O . R /O . R 

C 3 H 5 ^0 . R CHee-O- 



Vk \0 . R 

/C ^-°o^ oh : ,p=o 

\OH 

Since lecithin is optically active and as, according to Willstatter 
and Liidecke and also according to Power and Tutin, the glycero- 
phosphoric acid derived from lecithin possesses rotatory power, 
Ulpiani expressed himself in favour of the asymmetrical formula. 
Speculations of this kind are, of course, only of theoretical interest. 
Possibly the synthesis of the lecithins, which has not as yet been 
successfully carried out, will throw light on the question of the 
constitution of lecithin. Hundeshagen, as the result of an unsuc- 
cessful synthesis of lecithin, claimed to have proved the truth of 
Strecker's statement that lecithin was not a salt of di-stearyl-glycero- 
phosphoric acid and choline, but an ester-like combination of the 
two substances, in which the basic character of choline was retained. 
The choline salt of di-stearyl-glycerophosphoric acid obtained by 
Hundeshagen had quite different properties than lecithin. Kade's 
attempts to prepare lecithin synthetically must also be regarded as 
failures from a practical point of view. 

Occurrence of Lecithin. 

Lecithin is so widely distributed in the human and animal organ- 
isms that it has been concluded, though not without contradiction, 
that no organ exists which does not contain lecithin. Thus the 
phosphatide is found, according to Hermann, Hoppe-Seyler, 



Lecithin. 



( Am. Jour. Pharm. 
\ April, 1914. 



Manasse, Abderhalden and Peritz in the blood; according to 
Miescher in pus ; according to Gobley, Liebreich, Thudichum and 
Koch in the brain ; according to Dunham, Rubow, Krehl, Nerking, 
Heffter, Baskoff, Noel Paton, MacLean, BischofT and others in the 
heart (cardiac muscle), kidneys, suprarenal glands, liver, lungs and 
spinal cord, and according to Frankel in the pancreas, muscles, tes- 
ticles and submaxillary gland as well; according to Chevalier and 
Koch in nerve tissue (sciatic) ; according to Glikin, Rolle and 
Otolski in bone marrow ; according to Thudichum, Long and Gep- 
hart in bile; according to Dezani, Vacheron and Miescher in the 
sperm ; according to Donath in the cerebrospinal fluid ; according to 
Wallis and Scholberg in ascitic fluid, etc. Further, according to 
Hoppe-Seyler, it is a component of caviare; according to Burow, 
Tolmatscheff, Koch, Vageler, Siegfeld, Glikin, Dornic and Daire 
and Marre it is a component of milk and consequently of butter, as 
has been proved by Krampelmeyer, Jaeckl and Bordas. The per- 
centage of lecithin indicated by the various authors in human or 
animal organs is as follows : 



Blood 0.2 per cent. 

Blood corpuscles 0.46 per cent. 

per cent.) 
Brain 16 per cent. 
Heart 4.5 per cent. 
Cardiac muscle 12.5 per cent. 
Kidneys 8.5 per cent. 
Suprarenal gland 2.5 per cent. 
Liver 4.3 per cent 
Bile 0.15 per cent. 
Lung 1.5 per cent. 
Spinal cord 11 per cent. 
Marrow 3 per cent. 
Pancreas 0.5 per cent. 
Thymus 7.5 per cent. 



Human fat 0.05 per cent. 
Muscles 0.8 per cent. 
Testicles 1 per cent. 
Submaxillary gland 1 per cent. 
Nerve tissue 17 per cent. 

(of the dry tissue) 
Sciatic nerve 33 per cent. 

(of the dry tissue) 
Sperm 1.5 per cent. 
Milk 0.06 per cent. 
Butter 0.17 per cent. 
Yolk of egg 12 per cent. 
Rabbit (living) 0.5 per cent. 
Hedgehog (living) 0.8 per 

cent. 



1.8 



In the vegetable kingdom lecithin is also very frequently found. 
It was first discovered in plants by Knop in i860, but its general dis- 
tribution throughout the vegetable kingdom was first established 
by Topler. It is always abundantly present in seeds, buds and young 
shoots, a fact which indicates its great importance in the growth of 



Am. Jour. Pharm. > 
April, 1914. J 



Lecithin. 



169 



young plants. The lecithin content of various seeds is specially 
reported upon by Schulze, Forti, Maxwell, Bernardini and Chia- 
rulli ; lecithin in vegetable oils by Schlagdenhauffen and Reeb, Stell- 
waag, Jacobson, Riegel and others ; in sugar cane by Shorey ; in 
yeast by Hoppe-Seyler, Himberg and Sedlmayr ; in leaves, blossoms, 
fruits, etc., by Vageler ; in fungi by Heinisch, Zellner and Lietz; in 
grape pips and wine by Rosenstiehl, Funaro and Barboni, Muraro, 
Bicciardelli and Nardinocchi, Salvadori and Mazzaron ; and the 
occurrence of lecithin in the vegetable kingdom generally by 
Kraetzschmar, Heckel and Schlagdenhauffen, Stoklasa, Hanai, 
Marchlewski, Winterstein and Fliestand and others. 

The content of various seeds, vegetable oils, etc., is given as 
follows in the literature : 



Barley 0.7 per cent. 
Wheat 0.6 per cent. 
Rye 0.6 per cent. 
Peas 1.2 per cent. 
Lentils 1 per cent. 
Beans 0.8 per cent. 
Linseed 0.9 per cent. 
Vetch seeds 1.2 per cent. 
Lupin seeds 2 per cent. 
Pumpkin seeds 0.4 per cent. 
Poppy seeds 0.25 per cent. 
Maize 0.25 per cent. 
Soya-bean oil 0.15 per cent. 
Ergot 1.7 per cent. 
Toadstools 1.4 per cent. 
Yellow boletus 0.6 per cent. 
Mushrooms 0.9 per cent. 
Morel 1.6 per cent. 



Cantharellus cibarius 1.3 per cent. 
Lettuce 0.36 per cent. 
Rhubarb 0.33 per cent. 
French beans 0.25 per cent. 
Green peas 0.15 per cent. 
Green tomatoes 0.25 per cent. 
Yeast (dry) 2 per cent. 
Wine 0.03 per cent. 
Fat of melon seeds 0.6 per cent. 

" " lupin seeds 7.5-50 per cent. 
. " " peas 30-50 per cent. 

" " vetch seeds 13-21 per cent. 

" " rye 8 per cent. 

" " wheat 7 per cent. 

" " barley 7 per cent. 

" " oats 11.5 per cent. 

" " fenugreek seeds 1.5 per cent. 

" " maize 1.5 per cent. 



However, lecithin does not only occur as such, but especially in 
plants in combination with other substances. Thus ovo-vitellein, de- 
scribed by Hoppe-Seyler, is a combination of lecithin with albumin ; 
jecorin, described by Drechsel, Boskoff, Erlandsen and others, is a 
combination of lecithin with glucose or galactose and other sub- 
stances ; and protagon, which occurs in the central nervous system 
and in the brain and has been investigated and described by Lieb- 
reich, Hoppe-Seyler, Diakonow, Strecker, Gamgee, Blankenhorn, 



170 



Lecithin. 



f Am. Jour. I'liann. 
| April, 1U14. 



Baumstark, Ruppel, Kossel and Freytag, is a combination of leci- 
thin with cerebrosides. 5 Protagon is described by Kossel, Ruppel 
and others as a crystalline substance, soluble in hot alcohol and 
which swells up in water. 

Physiology of Lecithin. 

Special attention has been paid to the study of the origin and 
significance of lecithin in the vegetable world by Maxwell, Stoklasa, 
Staniski, Marchlewski, Hanai and Koch. Even though the results 
of their investigations have not rendered the chemistry of lecithin 
formation as clear as might be desired, yet they have shown that 
lecithin may and usually does occur in all parts of plants. From 
this fact alone it may be concluded that it is a very important or 
indispensable body in the plant. 

Maxwell attempted to prove that the phosphorus present in seeds 
in an organic form was changed during germination to the organic 
form, during which process lecithin was produced. The interme- 
diate stages passed through by the phosphoric acid are unknown. 
In the transition from the vegetable to the animal kingdom the 
organic combination is, in the author's opinion, retained. The 
lecithin of a hen's egg, on the other hand, changes when the egg 
is hatched into inorganic phosphorus compounds, and as a mineral 
phosphate plays a part in the bone-formation of the developing 
animal. But in the later stages of hatching, as Maxwell showed, 
the opposite process may occur. The most interesting fact brought 
out by Maxwell's researches is that the animal organism is capable 
of changing inorganic phosphorus into organic compounds. As in 
the opinion of some observers, to which reference will be made later, 
the lecithin ingested with the vegetable food is decomposed in the 
animal intestine and absorbed as phosphoric acid (glycerophosphoric 
acid), lecithin synthesis must occur in the animal and human organ- 
ism, for it would otherwise be impossible to explain the origin of the 
richness in lecithin of the animal organism. Reicher has recently 
also favoured this opinion. 

Stoklasa, from his own observations, formed the opinion that 
by far the greater part of the phosphoric acid of plants was present 



6 Cerebrosides are bodies containing nitrogen but no phosphorus, which 
on hydrolysis produce sugar. 



Am. Jour. Pharm. ) 
April, 1914. J 



Lecithin. 



171 



in the form of organic compounds. Besides the nuclein compounds, 
lecithin is an important example of this class. It probably plays an 
important part in the processes of assimilation and dissimilation. 
In testing the lecithin content of seedlings, leaves and blossoms, the 
author found that the lecithin was not decomposed by germination, 
but that no lecithin was formed except when, under the influ- 
ence of light and chlorophyll, carbonic acid assimilation had set in. 
He even showed that in the absence of chlorophyll (in the leaves) 
no lecithin is formed and that in etiolated seedlings the lecithin is 
used up or decomposed. It is possible that during the first vegeta- 
tive period lecithin, under the influence of light, assists in the for- 
mation of chlorophyll in the seedling. The greatest amount of 
lecithin is probably formed in fresh green leaves at the time when 
the function of assimilation is at its height, an assumption made 
probable by the fact that the amount of lecithin in leaf-buds is only 
half as great as that in fully developed leaves, and that it rapidly 
disappears as the leaves grow older; the chlorophyll is reduced and 
xanthophyll makes its appearance. According to this, there is a 
close connection between the formation of chlorophyll and lecithin. 
Stoklasa even considers that lecithin may be a product of assimila- 
tion in the chlorophyll corpuscle itself. In agreement with this 
conjecture is the observation that certain plants, if placed in the 
dark at the time of their most active growth, soon show a consid- 
erable diminution of lecithin in their leaves, as compared with those 
which are allowed to develop in the light. It has not yet been dis- 
covered in what way lecithin assists in chlorophyll formation, but 
according to Stoklasa, it is certain that no chlorophyll can be pro- 
duced in the absence of light and phosphorus. Thus' even if lecithin 
is not a part of the chlorophyll corpuscle itself, as was formerly 
assumed by Marchlewski, yet it appears to participate in chlorophyll 
formation and to supply the necessary phosphorus. From the 
leaves lecithin travels by way of the stems into the blossoms, where 
it may perhaps assist in fertilisation, and thence by the fruits into 
the seeds. It is by no means certain, however, that the green leaves 
are the sole producers of lecithin ; it is quite probable that plants 
and animals are able to build up lecithin in certain organs and from 
certain substances, as is the case for example in yeast and in fungi. 

Stoklasa' s observation that phosphorus is present in plants chiefly 
in organic form is confirmed by the results of Staniski's researches. 
This observer found only very small amounts of inorganic phos- 



172 



Lecithin. 



{Am. Jour. Pharm- 
April, 1914. 



phoric acid in the seeds of 'millet in comparison with the amount of 
organic phosphorus present. He found that in millet lecithin for- 
mation was at its height during the period of seed development, and 
that the maximum amount of lecithin was contained in the plant 
during the period of panicle formation. Thus it is justifiable to 
draw the conclusion that lecithin has important functions to perform 
in connection with flower and seed formation. 

Hoppe-Seyler pointed out the close relationship between lecithin 
and chlorophyll mentioned above. He even placed chlorophyll in 
the group of lecithins. Although this view has not as yet been con- 
firmed, it is supported to some extent by Stoklasa's researches. 
Furthermore, Marchlewski, Bode and Kohl have put forward theo- 
retical considerations according to which chlorophyll represents a 
lecithin in which the fatty acid radicles 6 are replaced by special, 
colored complexes (chlorophyllanic acids), or these complexes 
themselves are chlorophyll combined with lecithin. 7 

Hanai's statements supplement Stoklasa's communications. He 
made the observation that the old, green leaves of Thea Chinensis 
lose their lecithin in spring, and that the young, growing leaves are 
very rich in lecithin. He therefore places lecithin among the re- 
serve substances, which are stored in certain parts of the plant (as, 
for example, in the bark of the plant just mentioned) until the next 
period of growth, when they are supplied to the new shoots. 8 

The conclusions drawn by Vageler from his investigations are 
deserving of special mention. According to these, the lecithins are 
inseparably bound up with metabolism and with the vital processes 
of the plant generally. The content of phosphatides increases up to 
the time of development of the fruit, the zenith of development, and 
decreases as the fruit ripens. Lecithin has, in the author's opinion, 

11 Compare the formula for lecithin on page 164. 

7 According to W. Pfeffer (Pflanzenphysiologie, 1897, 2nd edition, Vol. 
1. p. 478). the lecithins are perhaps necessary for the construction of proto- 
plasts. However, it is not yet known whether they take part in the con- 
version of fats. The occurrence of choline in plants probably depends upon 
the conversion of lecithin. According to Willstatter, chlorophyll contains 
no phosphorus, whereby the theories of the authors mentioned above are in- 
correct. Compare also Marchlewski, Biochemische Zeitschrift, 1908, Vol. 
10, p. 131. 

8 According to Jost (Pflanzenphysiologie, 1908, p. 184), however, the leci- 
thins are not reserve substances, but constructive materials for protoplasm, 
and for this reason they are not decomposed during germination of the seeds. 



Am. Jour. Pharm. ) 
April, 1914. j 



Lecithin. 



173 



probably nothing to do with fat, with which others often consider it 
to be in relation. Like Koch, he seeks the function of lecithin in the 
cell primarily as an oxygen carrier, but also in the colloidal char- 
acter of the phosphatides, " for the substratum of life itself, proto- 
plasm, which is still in many respects so enigmatical, is a colloid." 

The physiological significance of the fatty acids contained in 
lecithin and of choline is explained by Koch. According to him, 
the lecithins are of importance for the life of the celi in two< ways. 
For in conjunction with the albumins in colloidal solution, they con- 
stitute the basis for the formation of the necessary viscosity, on 
account of the ease with which they are influenced by ions (Na, Caj. 
Further, by means of their unsaturated fatty acids they take part 
in oxygen metabolism, and by their methyl groups, which are com- 
bined with nitrogen, in other reactions not yet known. Phosphoric 
acid, although in some respects the nucleus of the whole, does not, 
in Koch's opinion, play any part in metabolism ; Halliburton has 
shown that the amount of phosphorus in degenerated nerves does 
not begin to decrease before the eighth day. The author explains 
the fact that the residues of the unsaturated fatty acids are capable 
of taking part in oxygen metabolism by the ease with which they 
are oxidised ; this is also known to be the case with lecithin which 
has been in contact with the air for some time. But it has not yet 
been proved that the lecithins may be regarded as oxygen carriers. 
The physiological significance of the nitrogen group may, according 
to Halliburton, be recognised by the fact that in certain diseases of 
the nervous system, such as general paralysis, a considerable amount 
of choline passes into the cerebrospinal fluid. 

As in the vegetable kingdom, so in the animal kingdom, lecithin, 
as I mentioned above, is present in almost every organ. It is present 
in comparatively large amounts in the principal organs, and the 
conclusion may consequently be drawn that it also performs impor- 
tant functions in the economy of the animal cell. The nature of 
these functions cannot be stated with certainty. Nor has it been con- 
clusively ascertained whether lecithin is formed in the animal or- 
ganism, whether it is ingested with the food, or whether both these 
processes take place. The results of the investigations of various 
observers afford some elucidation of the matter. 

Bokay found that lecithin was split up in the intestine by the 
fat-splitting ferment of the pancreas, or putrefactive ferment, into 
fatty acids, choline and glycerophosphoric acid. As he was unable 



Lecithin. 



J Am. Jour, tharm. 
\ April, 1914. 



to demonstrate the presence of phosphoric acid in ethereal and 
alcoholic extracts of the faeces, he concluded that lecithin or its 
decomposition products were absorbed and used up by the organism. 
In agreement with this conclusion is the fact investigated by him 
that the amount of phosphoric acid in the urine is substantially in- 
creased after the ingestion of lecithin. Glycerophosphoric acid is 
absorbed from the intestine in the form of a salt, and is not, accord- 
ing to Hasebrok, further broken down into glycerin and phos- 
phoric acid. Grosser and Husler, on the other hand, think it im- 
probable that glycerophosphoric acid passes directly from the intes- 
tine into the organism, as they succeeded in isolating a ferment, the 
so-called glycerophosphotase, from the intestinal and renal cells 
which splits up glycerophosphoric acid without leaving a residue. 
They therefore assume that lecithin is completely broken down in 
the intestine and is built up again from its elements in the tissues. 
The fatty acids, like the fats taken in with the food, are partially 
absorbed in the form of salts of fatty acids and partially excreted. 
Choline is further broken down with formation of carbonic 
acid, ammonia and methane. As lecithin is said to be com- 
paratively readily broken down, it is probably safe to assume that 
lecithin is not absorbed as such in the intestine ; but this does not 
prove that it may not be partially absorbed unaltered and carried 
to the circulation. Miescher's observation on Rhine salmon is gen- 
erally cited as a typical example of lecithin formation in the animal 
organism. According to this, a comparatively large amount of 
lecithin is formed in the sexual organs of these fishes during the 
hunger period, which is said to occur as they wander up stream. 
The necessary phosphorus is presumably supplied by certain muscles 
of the fish. Paton also attempted to prove that in salmon inorganic 
phosphorus changes into organic phosphorus ; however, the asser- 
tions of Paton and Miescher can only be accepted if it be proved 
that during their sojourn in fresh water these fishes really take in 
no nourishment. This was doubted by Putter. Rohmann, from 
experiments on mice, concludes that the animal organism is capable 
of forming lecithin, for the mice increased and continued their de- 
velopment on lecithin-free food. But in similar experiments car- 
ried out by Stepp and Rohl the experimental animals perished. 
According to Rohl, mice fed exclusively on rice always perish 
in a few weeks, whereas on the addition of a small amount of 
lecithin their development continues normally. He therefore con- 



Am. Jour, riiarm. 1 
April, 1914. J 



Lecithin. 



175 



siders lecithin to be an essential component of food, which cannot 
be constructed from its elements in the mammalian body. On the 
other hand, according to Fingerling's observations, ducks are appar- 
ently able to produce large amounts of lecithin from inorganic phos- 
phorus. It must also' be assumed that glycerophosphoric acid which 
has been absorbed is made use of in certain organs for the produc- 
tion of lecithin. The choline required for this purpose has been 
shown to be present in various parts of the organism (Kinoshita °) . 
Mulon, Bernard and others point to the suprarenal glands as the 
seat of formation of lecithin. Moreover, lecithin appears to be 
capable of being split up by ferments in certain organs. Coriat, 
for example, believes an enzyme to be present in the brain, which 
decomposes lecithin with separation of choline. He did not succeed 
in isolating this enzyme, but he proved that its action was destroyed 
by heating. 

After Bokay had demonstrated that lecithin could be split up 
by the secretion from the small intestine, P. Mayer attempted to 
establish which of the ferments of the small intestine (trypsin, erep- 
sin, lipase) caused this disintegration. He found that lecithin was 
abundantly split up by steapsin and that under certain conditions 
the fatty acids separated in a crystalline form. According to this, 
the behaviour of lecithin is identical with that found by Connstein in 
the fermentative decomposition of the true fats. Mayer believes 
his observations to show that the enzymes do not react in the same 
way upon d- and 1-lecithin. 

SchumofT-Simanowski and Sieber also confirm the action of 
pancreatic and g*astric 'steapsin in splitting- up lecithin, whereas 
their tests, with lipase of blood or blood serum gave a negative re- 
sult. It is not capable of splitting off fatty acids from lecithin. It 
is indeed possible, with the help of this negative character, to dis- 
tinguish lipase from other lipolytic enzymes. Lecithin is, on the 
other hand, decomposed by vegetable ferments, especially by the 
ferment of Ricinus communis, with separation of fatty acids. 

But the results of the authors mentioned above do not appear to 
correspond entirely with all the facts, if they are compared with 

Choline is said by Lohmann to occur in the suprarenal glands, by von 
Fiirth and Schwarz in the thyroid gland and intestinal extracts, by Schwarz 
and Lederer in the thymus, spleen and lymphatic glands, by Kutscher in flesh, 
by Letsche in serum, by Jacobsen in bile, by Cramer in the brain, by Bohm 
in the placenta, by Gautrelet in the kidneys, ovaries, testicles and pancreas. 



176 



Lecithin. 



Am. Jour. Pharni. 
April, 1914. 



the results obtained by Slowtzoff, Stassano and Billon. According 
to these authors, lecithin is not by any means readily decomposed and 
it is doubtful whether it is decomposed by the action of putrefactive 
bacteria and pancreatic ferment. Thus Stassano and Billon found 
that neither activated pancreatic juice nor gastric juice acts upon 
lecithin; this was confirmed by SlowtzofT for fresh lecithin, but he 
observed the decomposition of older (oxidised) lecithin. He also 
confirmed the observation that choline was separated from lecithin 
which had been stored for some time, even when boiled, alkaline 
ferment solution was used. Independently of the separation of cho- 
line, saponification of lecithin by means of pancreatic juice, — e.g., 
by steapsin, apparently occurs. As lecithin is readly emulsified in 
the presence of bile and albumoses, and as Stassano and Billon 
claimed to> have observed that lecithin, when injected subcutaneously, 
was taken up by the leucocytes which had migrated to the site of 
injection, and that by feeding on lecithin the latter apparently passed 
into the lymph of the thoracic duct, SlowtzofT conducted experiments 
which showed that lecithin, when administered internally, is in part 
ingested unchanged, as could be recognised by the appearance of 
lecithin in the lymph. As regards the splitting up of lecithin in the 
intestine, it occurs, according to SlowtzofT, in the duodenum where 
it cannot, in his opinion, be caused by putrefactive bacteria. 

The results of the investigations of the observers mentioned 
above lead to the assumption that the lecithin taken in witji the 
food is partly absorbed as such and partly split up. SlowtzofT as- 
sumes that like the fats it can be gradually reconstructed in the 
organism by synthesis. The proof of this may be sought in the fact 
that the same or very similar results have been achieved in therapy 
with the salts of glycerophosphoric acid (compare Merck's Report 
191 1, pages 1 to 30) as with lecithin. 

With regard to the action on lecithin and its decomposition by 
ferments (lipase, diastase) reference may also be made to the pub- 
lications of Lapidus and Terroine. 

The investigations carried out by Glikin are of much value for 
the biological significance of lecithin. He points out that birds and 
mammals show a greater or less content of lecithin in the bones or 
the whole body, according as to whether they are born naked and 
helpless, or independent and with their senses developed. Thus the 
amount of lecithin in cats and dogs, which are born blind and help- 
less, is greater than that in guinea-pigs, which immediately after 



A in. Jour. Phariii. ( 
April, l'J14. / 



Lecithin. 



177 



birth are able to feed on cabbage and turnips like the fully devel- 
oped animals and are not dependent upon mother's milk; similarly 
insessorial birds contain more lecithin than autophagous birds, which 
is indeed clearly shown in the eggs of these birds. Man, also, 
who comes into the world helpless, shows a very high percentage of 
lecithin in the bone marrow, which is only appreciably diminished 
when growth proceeds more slowly, or ceases. He also established 
the fact that the bone marrow of young animals contains far more 
lecithin than does that of fully developed animals, and that this 
store of lecithin diminishes as the animal grows and that new- 
born animals come into- the world with a large supply of lecithin. 
From these observations it is evident that lecithin represents a 
highly significant factor in the growth of animals, even though 
nothing is yet known of the finer biological processes involved in the 
utilisation of lecithin in the cell and in the organism. 

But in order to form a conception of the functions of the lecithins 
or of the lipoids in general, the colloidal nature of these substances 
must primarily be taken into account; and also their capability 
of forming solutions and compounds, which are readily decomposed, 
with other substances of importance in the construction and the life 
of the cell. It must also be taken into' consideration that certain 
concentrations of lipoids are more soluble in solutions of alkaline 
salts than in other salt solutions. It is assumed that by an increase 
in the concentration of the salt by the entrance of calcium salts into 
the cell with consequent separation in flakes of the lipoids, mem- 
branes are formed which are permeable, impermeable or semi-per- 
meable to certain solutions. The so-called semi-permeable mem- 
branes, especially, appear to be of importance to the life of the cell, 
as they serve to keep within bounds the entrance and exit of sub- 
stances. 

In the interior of the cell, according to Meyer, it is through the 
intervention of the lipoids that the whole of the contents do not join 
to form a homogeneous mass, but that the thousand particles form- 
ing the cell, with all their different chemical affinities, remain side 
by side, drawn up in order and at a measured distance ; on the sur- - 
face, however, they constitute a guard against too rapid streaming 
in and out of water, and against the penetration of all the salts 
dissolved in the blood and in the tissue fluids, and of other sub- 
stances. They also form a sort of sieve for the penetration of sub- 
stances soluble in fat, especially of those which dissolve more readily 



i 7 S 



Lecithin. 



Am. Jour J'lianii. 
April, 1914. 



in lipoids than in water and aqueous albumin-colloids. The action 
of narcotic drugs stands in close relation with this solubility in 
lipoids. It may also be assumed that the functions of the lipoids 
may, within certain limits, be modified by their different chemical 
construction, and solubility in the body juices, as well as by reciprocal 
solution. For it is known that the solubility of the best known 
lipoids, lecithin an.d cholesterin, may be altered in other fluids by 
mixing the two substances. Erlandsen found that lecithin, which 
by itself is insoluble in acetone, became soluble to a slight degree in 
the presence of cholesterin. It must further be taken into considera- 
tion that the lecithin of the organism includes a large number of 
similarly constructed substances, which occur in mixtures in various 
proportions, and on account of the varying concentrations of salt 
solutions are differently influenced and precipitated or redissolved. 

The permeability for albumins and inorganic (calcium, alkali 
and phosphoric acid ) salts of the semi-permeable membranes formed 
by the lipoids, which is confirmed by the fact that the organic lipoids 
contain inorganic salts of this kind, facilitates the perception of the 
electrical processes which, in the opinion of various observers, take 
place in the cell. Thus Hober and Nernst have developed theories 
which are intended to explain the connection between galvanic proc- 
esses in the organ tissues and the stimulation of nerve activity. 

The physiological processes which take place in the cells between 
lecithin and narcotic drugs are of great pharmacological interest. 
Harlen and von Bibra considered the narcotic action of ether and 
chloroform to be due to the liberation of fat by these drugs in the 
cells of the brain. Hermann assumed that the narcotic drugs ^at- 
tacked the lecithins and cholesterins of the ganglion cells. H. 
Meyer came nearer to the truth when he ascertained that the action 
of a narcotic drug- was the more powerful the more readily it dis- 
solved in lipoids and the less readily it was soluble in water. This 
was also confirmed by Overton. In his opinion the narcotic drugs 
pass into those components of the cell which contain cholesterin 
and lecithin, and alter their physical condition in such a way as to 
disturb their functions, or to act injuriously upon the functions of 
other components of the cells. This alteration of function very 
probably depends upon a sort of anchoring of the narcotic to the 
lipoids, the bond being weakened by the introduction of other lipoids. 
This at least follows from Nerking's experiments. This observer 
administered to animals simultaneously intravenous injections of 



And. Jour. l*harru. | 
April, 1914. / 



Lecithin. 



1 79 



lecithin and urethane and found that the usual prompt action of 
urethane remained absent. He concluded that urethane, injected 
simultaneously with the lecithin, became anchored to the latter and 
was thus unable to enter into reciprocal action with the lipoids of 
the brain. Further experiments with ether, chloroform, morphine, 
scopolamine, novocaine, tropacocaine and stovaine gave a similar 
result. The subcutaneous, intravenous and intraperitoneal injec- 
tion of these narcotics, applied simultaneously with lecithin, always 
caused an earlier return to consciousness, or the earlier reappear- 
ance of sensation. Similarly, animals which had previously received 
an injection of lecithin required a larger dose of the narcotic than 
those which had not previously undergone lecithin treatment. These 
results justify the conclusion that lecithin injections might be em- 
ployed for human beings also, in order to shorten the period of 
narcosis or as a prophylactic against its troublesome secondary 
effects. For experiments of this nature subcutaneous injections of 
aqueous emulsions of lecithin or intravenous injections of lecithin- 
sodium chloride emulsions are suitable. 

The part played by lecithin in haemolysis by poisons is also of 
physiological significance. In 1902 Flexner and Noguchi made the 
observation that blood corpuscles, which had been completely freed 
from the adherent serum by washing with physiological salt solu- 
tion, were not dissolved by snake venom. They assumed that a 
substance was present in the blood serum which played the part of 
activator of the amboceptors of the snake venom, and this was later 
experimentally demonstrated by Kyes. According to Kyes, cobra 
venom which is inactive towards various kinds of blood immediately 
assumes hemolytic properties on the addition of lecithin. If cobra 
venom occasionally causes solution of blood corpuscles in spite of 
the absence of serum, it is due, according to< Kyes and Sachs, to the 
lecithin contained in the blood corpuscles ; and this occurs more 
readily the more loosely the lecithin is bound to the blood corpuscle 
or to the molecule of protoplasm. The communications of Abder- 
halden and le Count show that the activating properties of lecithin 
may be arrested by cholesterin. 

Finally, the relationship existing between the action of lecithin 
and that of Rontgen rays or radium rays has gained the considera- 
tion of physiologists. Reference may be made to the communica- 
tions on this subject by Schwarz, Werner, Exner, Sywek, Neuberg, 
Wohlgemuth and Hoffmann. 



i8o 



Lecithin. 



( Am. jour. Pharm. 
[ April, 1914. 



The Importance of Lecithin in Metabolism and Nutrition. 

After the favourable effect of lecithin upon phosphorus metab- 
olism and upon nitrogen metabolism had been established, first by 
Selenski and later by Serono and Charrin, Desgrez and Zaky, ex- 
perimenting on animals, proved that feeding with lecithin leads to 
a lasting retention of phosphorus. According to their observations, 
phosphorus is used for bone-formation and for building up the 
brain; they were also able to prove that after feeding with lecithin 
the amount of lecithin in the brain was appreciably increased. The 
favourable influence exerted by lecithin upon metabolism in general 
and upon retention of phosphorus in particular, led the two observers 
to undertake more exhaustive observations on guinea-pigs, in which 
they found that it was not the glycerophosphoric acid, but the choline 
which diminished the excretion of phosphorus and causes an in- 
crease in the body-weight, — e.g., that the action of lecithin depends 
upon its basic components. Hatai was able to confirm the favourable 
influence exerted by lecithin upon growth. He treated white rats 
belonging to one and the same brood, some with lecithin and some 
without, and obtained the surprising result that the animals treated 
with lecithin thrived considerably better, indeed they increased in 
body-weight by 60 per cent, more than the other animals. Internal 
administration brought about the best results, but better growth 
of the animals was also observed after subcutaneous administration. 

Danilewski noticed that tadpoles grew with extraordinary 
rapidity under the influence of lecithin, and he therefore tried the 
drug in young dogs. He found that the subcutaneous and internal 
administration of lecithin is a great incentive to bodily growth, im- 
provement of the blood and increase of the brain, which he explains 
as an acceleration of the bioplastic, morphogenous processes. He 
observed especially that the dogs treated with lecithin appeared 
much more lively, more intelligent and physically stronger than 
the control animals. For his experiments he employed an emulsion 
of lecithin in physiological salt solution, of which he injected doses 
of 0.02 to 0.05 gramme of lecithin under the skin of the abdomen, 
or gave double this dose by mouth. In further experiments on the 
blood-forming properties of the spleen and the bone marrow, 
Danilewski and Selenski arrived at the conclusion that lecithin plays 
an important part in the haematopoietic processes which take place 
in these organs. This assumption gains in probability when it is 



Am. Jour. Pharm. ) 
April, 1914. | 



Lecithin. 



181 



borne in mind that lecithin is capable of adsorbing and binding in 
the organism various substances of importance in the vital process, 
•such as albumins, sugars, salts, ferments, etc., substances which for 
their part are readily decomposed into- their components. 

An insight into the relations which exist in metabolism under the 
cooperation of lecithin is also furnished by the results of the inves- 
tigations of Franchini, Massaciu, Buchmann, Zuntz, Yoshimoto and 
Slowtzoff. According to Franchini, feeding rabbits on lecithin in- 
creases the lecithin content especially in the liver, less in the muscles 
and not at all in the brain. The increase in the lecithin content of 
the liver remains for some time, even after the ingestion of lecithin 
has been discontinued. The discovery of the author that only very 
little lecithin is excreted in the faeces tallies with other statements 
which have been mentioned above. Franchini also' confirmed the 
observation that during lecithin administration an increased amount 
of glycerophosphoric acid is found in the muscles and in the liver. 
He also' found a slight increase of this acid in the urine, though this 
may have been first formed from lecithin in the urine, for lecithin 
is a somewhat labile substance. The fact that no choline could be 
found in the urine is, however, not in favour of this view. 

The choline which is split off from the lecithin during metab- 
olism is, according to the author, further broken down and oxi- 
dised in the organism, and appears as formic acid in the urine. 
Another hypothesis which has not yet been proved has been sug- 
gested by Low. He assumes that lecithin acts in metabolism as a 
fat-carrier, the fatty acids being split off from the molecule and then 
replaced by new ones. Part of the lecithin-phosphorus is, accord- 
ing to Yoshimoto and Buchmann, kept back for some time in the 
organism and is most probably only very gradually excreted. Be- 
sides retention of phosphorus, Yoshimoto, Zuntz and Slowtzoff also 
found retention of nitrogen, which was not always accompanied by 
an increase in body-weight. Voltz and Massaciu also observed an 
increase in the albumin content after feeding dogs and guinea-pigs 
on lecithin, whereas Rogozinski was unable to demonstrate either 
an increase in nitrogen or phosphorus. 

These experiments on animals, the results of which are in part 
contradictory, have long been rendered perfectly clear by means of 
the practical employment of lecithin in man. The investigations on 
metabolism carried out by Cronheim and Miiller on several children 
(under a year old) are interesting. On feeding with children's 



Lecithin. 



Am. Jour. Pharm. 
April, 1914. 



meal (consisting of skim milk powder, oatmeal and sugar) and 
administering lecithin, the nitrogen of the food was better assimi- 
lated and retained by the body than was the case when lecithin wa$ 
not administered simultaneously. In the former case the nitrogen re- 
tention amounted to 19 to 28 per cent., in the latter case only to 2 to 
24 per cent. On the other hand, as regards phosphorus retention, food 
containing lecithin showed no advantages, nor could any influence 
on fat and carbohydrate metabolism be observed. Calcium and mag- 
nesium salts were, however, held back by the lecithin, which is a 
point in favour of increased bone-formation. The older the chil- 
dren, the more evident was the favourable influence of lecithin. This 
phenomenon is perhaps due to the fact that the body of the suckling 
contains, according to SiwertzerT, a large store of lecithin, which is 
gradually used up in the course of the first 4 to 5 months of life. 
Thus, children under 5 months of age are so richly supplied with 
lecithin that a further supply becomes superfluous and cannot be 
utilised. The utility of the drug really first becomes apparent when 
the store of lecithin has been exhausted. 

Recent experiments by Cronheim show that lecithin is not only 
valuable during growth, but is also of value to adults. A fully 
developed individual requires a certain amount of lecithin for the 
maintenance of normal metabolism. It is therefore justifiable to 
assume that the drug is as beneficial for adults as for children. 

Massaciu carried out the following metabolism experiment on a 
man : he was first given meat and no lecithin, in the second experi- 
mental period he received roborat containing lecithin, and in the 
third period he was given both meat and lecithin. The assimila- 
tion of nitrogen was increased threefold in the second period as 
compared with the first, the nitrogen being better utilised in the 
intestine. The same occurred in the third period. This furnished 
a further proof of the nitrogen-sparing power of lecithin. The 
author also observed retention of phosphorus during lecithin admin- 
istration. Marfori's results are in agreement with this; he found 
that egg-lecithin, when subcutaneously applied, furnished the or- 
ganism with phosphorus capable of being assimilated. 

Moricheau Beauchamp experimented on himself and on a med- 
ical student and found a nitrogen-sparing and phosphorus-sparing 
action. The author administered 0.5 to 1 gramme of lecithin a day 
and found after 4 days that he had gained in energy and that his 
weight had increased by 900 grammes. In the urine he found a 
decrease of nitrogen, urea, phosphoric acid and xanthin bodies. 



TAKr-} Lecithin. 183 

The value of lecithin in nutrition is also shown in a paper by 
Usuki. The author found in. experiments on dogs that lecithin has 
a favourable influence on the saponification of neutral fat, and that 
it thus accelerates the digestion of fat. As regards digestion in 
general, the only doubtful point is whether lecithin exerts a favour- 
able or a harmful influence upon it, or upon the digestive ferments. 
This point has not yet been settled. Certain conclusions may, how- 
ever, be drawn from the communications of Hewlett, Furth, Schiitz, 
Kiittner, KalaboukofT and Terroine. Furth and Schiitz found that 
bile has the power of augmenting the action of the fat-splitting 
and albumin-splitting pancreatic ferments, which they consider to 
be closely connected with the presence of bile salts. Nencki had 
previously made a similar observation. Hewlett, on the other hand, 
considered the favourable influence upon these ferments to be due 
to the lecithin content of bile ; Furth and Schiitz were only able to 
confirm this in the case of an alcoholic solution of lecithin. Kiittner 
attempted to test more carefully the influence of lecithin upon the 
digestive ferments ; he came to the conclusion that definite additions 
of lecithin sometimes hasten and sometimes delay the enzyme action 
of gastric or pancreatic juice. He was, however, unable to offer a 
reliable explanation of the matter. KalaboukofT and Terroine 
have expressed the decided opinion that diastatic ferments are 
not influenced by lecithin. The results of their investigations are 
as follows: "The addition of lecithin to pancreatic juice never 
hastens its decomposing action on monobutyrin ; it hastens very 
slightly the action upon oil, but only in relatively high concentra- 
tions. The lipolytic action of glycerin extracts of gastric mucous 
membrane remains unaltered by the addition of lecithin ; intestinal 
lipase is unaltered by the addition of lecithin. The addition of 
lecithin has no effect upon the rapidity of starch hydrolysis, of diges- 
tion of casein and coagulated albumin, or upon the coagulation of 
milk and pancreatic juice." These results throw doubt upon Hew- 
lett's view mentioned above. The communications of Bang, Wohl- 
gemuth, Lapidus and Starkenstein also show that lecithin does not 
possess the accelerating action assigned to it by Hewlett. 

Slowtzoff, as a result of his lecithin experiments on man, came 
to the conclusion that lecithin occasioned retention of nitrogen, ac- 
companied by a diminution of sulphuric acid excretion in the urine. 
He considers this to be related to the decomposition of albuminous 
bodies, and concludes that what occurs is retention of albumin and 
not retention of other nitrogenous products (extractives). In his 



184 



Book Reviews. 



f Am. Jour. Pharm. 
t April, 1914. 



opinion, the assimilation of albumin runs parallel with the assimila- 
tion of phosphoric acid and the diminution of the albuminous sub- 
stances. This phenomenon shows that lecithin promotes the organi- 
sation of albumin, — e.g., its transformation into tissue-albumin. 
This transition of absorbed into organised albumin must, accord- 
ing to Umikoff and SlowtzofT, be considered as being due to the 
addition to the albumin of phosphoric acid and xanthin bodies. 
Thus, according to SlowtzofT, lecithin acts favourably upon this or- 
ganisation, and it is comprehensible for the increased assimilation 
of albumin to be accompanied by the retention of xanthin bodies 
and of phosphoric acid. 



BOOK REVIEWS. 

Allen's Commercial Organic Analysis. Vol. III. Enzymes, 
Proteins and Albuminoid Substances, Milk and Milk Products, Meat 
and Meat Products, Haemoglobin and Blood, Proteids and Fibroids. 
Edited by W. A. Davis and Samuel S. Sadtler and the following 
contributors : E. F. Armstrong, S. B. Schryver, L. L. van Slyke, 
Henry LefTmann, Cecil Revis, W. D. Richardson, J. A. Gardner, 
E. R. Bolton, G. A. Buckmaster, W. P. Dreaper and Jerome Alex- 
ander. Philadelphia: P. Blakiston's Son & Co., 1012 Walnut Street. 
1913. $5.00 net. 

This is another volume of Allen's Commercial Organic Analysis 
which contains very much matter of special interest to pharma- 
cists. Indeed, every article contains information that is likely to be 
wanted either for purposes of manufacture or in analytical work. 
The article on haemoglobin and its derivatives, by John A. Gardner 
and George A. Buckmaster, is one of the most succinct articles on 
the practical examination of blood that we have seen. A similar 
commendation may be made of the articles on " Proteins of Milk," by 
L. L. van Slyke, " Milk," by Dr. Henry LefTmann, " Milk Prod- 
ucts," by C. Revis and E. R. Bolton, and " Meat and Meat Products," 
by W. D. Richardson. 

In addition to the article on the " Proteins of Milk " there are 
two other chapters on these highly complex nitrogenous substances. 
The one on " The Proteins and Albuminoid Substances " by S. B. 
Schryver and the other on " Proteins of Plants " by J. Frankland 
Armstrong. While the monograph on plant proteins may not con- 



Am. Jour. Ptiarrn. > 
April, 1914. j 



Current Literature. 



185 



tain as much general information as the work of T. B. Osborne on 
" The Vegetable Proteins, " yet it contains, probably, the essentials 
for all analytical work. 

Among the other valuable articles are those on " Enzymes " by 
E. Frankland Armstrong and on " Albuminoids in Scleroproteins " 
by Jerome Alexander. In some respects, this chapter on the albu- 
minoids by Mr. Alexander is one of the most interesting in the whole 
volume. The word albuminoid is restricted by the biological chem- 
ists of America to simple proteins which exhibit pronounced insolu- 
bility in all neutral solvents. On the other hand, as many of these 
protein substances form the chief constituents of the skeleton of 
animals as well as of the skin and its appendages, the physiological 
chemists of England apply the term scleroproteins to them. Alex- 
ander classifies these substances as follows: (1) Collagens or jelly- 
forming albuminoids; (2) Fibroids; (3) Chitinoids ; and (4) 
Keratins. 

CURRENT LITERATURE. 
Formalized Gelatin Capsules. 

Enteric Capsules (Hard and Soft Gelatin). — Used for medi- 
cines which are apt to produce gastric disturbance, such as Potas- 
sium Iodide, Oil of Santalwood, Sodium Salicylate, Sodium Car- 
bonate, Creosote, Sodium and Zinc Phenolsulphonate, etc. 

Ballenger and Elder suggest the immersion of the filled capsule 
for one minute in a dilution of 1 part of 40 percent. Formaldehyde 
Solution in from 40 to 60 parts of water. The capsules should be 
allowed to stand for two weeks after immersion before use. 

Another method is to subject the filled capsules to the vapor of 
Solution of Formaldehyde as follows : 

Place the capsules in an open box in a vessel which can be tightly 
closed. Take 15 Cc. of 40 percent. Formaldehyde Solution for each 
cubic foot of space in the vessel and pour it on cotton or gauze 
spread out upon a dish in the vessel. 

Six hours' exposure to the vapor is sufficient for capsules which 
are not to be used immediately. Twelve hours' exposure is prefer- 
able for capsules required for immediate use. These estimates are 
for soft elastic capsules kept at room temperatures (from 70 to 
75° F.). 



Current Literature. 



{Am. Jour. Pharm. 
April, 1914. 



Another plan suggested to secure intestinal absorption is to in- 
corporate the medicament in a mixture of suet and paraffin. The 
stomach contains no fat digestant and the mass will pass into the 
intestines. The following combination is suggested : 

Sodii Carbonatis Monohydratis or 
Potassii Iodidi or 

Sodii Salicylates 90 Gm. 

Sevi 30 Gm. 

Paraffini 16 Gm. 

M. ft. mass. 

Melt all ingredients together on a water-bath and encapsulate 
in No. 00 gelatin capsules. 

To test the efficiency of the method prepare test capsules of 
methylene blue and oil of santol. 

Two hours after administration the eructation following the 
taking of a carbonated water will indicate whether or not the capsule 
has broken in the stomach. If the capsules have been hardened too 
greatly by the formaldehyde, the fact will be indicated by very slow 
coloring of the urine by the methylene blue. 

Mr. Smith, in his Thesis, advises the placing of the filled cap- 
sules in a ten percent, solution of formaldehyde during fifteen 
minutes, then washing them in running water for twenty minutes. 
The capsules are afterward dried in a dish in a water-bath for five 
hours or until free from the odor of formaldehyde. They have been 
used, in his experience, for the administration of Sodium Phenosul- 
phonate and Zinc Phenolsulphonate. (See Thesis of N. L. Smith, 
P. C. P., 1912, vol. 5 ; also Ballenger and Elder, in lour. A. M. A., 
1914, p. 197.) 

E. F. Cook. 
Deterioration of Nitroglycerin Tablets. 

Rippetoe & Smith (Journal A. Ph. A., January, 19 14, 96) report 
the results of several experiments which lead them to conclude that, 
" nitroglycerin will volatilize in the process of making the tablets if 
the granulation is exposed for any length of time, but after com- 
pressing the tablets and storing in ordinary corked bottles very 
little deterioration takes place. 

" The tablets will lose in strength if exposed in unstoppered 
bottles, therefore containers that are not air tight, such as cardboard 
boxes, should not be used." 



Am. Jour. Pharm. * 
.April, 1914. I 



Current Literature. 



187 



The assays were made by the modified Scoville method, which 
they consider to be a very practical and reliable method. 

"Samples of 0.01 (1/100) and 0.02 (1/50) grain hypodermic 
tablets, which were assayed on April 12, 191 2, having been made 
some time previous, were set aside on a laboratory shelf in ordinary 
cork stoppered glass tubes of 100 each. These tablets were assayed 
by the modified Scoville method on November 12, 19 13, with the 
results as shown in the following table : 

April 12, 1912. November 12, 1913- 

0.02 grain 0.0150 grain 0.0149 grain 

0.01 grain 0.0061 grain 0.0057 grain 

''These tablets while they were deficient in nitroglycerin when 
made show practically no loss during a period of 19 months. 

" A 10 per cent, solution of nitroglycerin (strength was not con- 
firmed by analysis) was mixed with sugar of milk to give a nitro- 
glycerin content of 5 per cent. This mixture upon analysis was 
found to contain 4.13 per cent, of nitroglycerin. A quantity of 
hypodermic tablets was made up from this mixture using the theo- 
retical amount based upon the above analysis to give a tablet assay- 
ing 0.01 grain. The tablets upon assaying were found to contain 
0.0102 grain nitroglycerin. These tablets were handmade while 
a lot of tablet triturates, which were made from a granulation on p. 
machine using the same quantities as above, assayed 0.0093 g ra i n 
nitroglycerin. 

" Two bottles each containing about 100 of 0.02 grain tablet 
triturates, made in 1907, were set aside in a closet, one of the bot- 
tles being corked and the other having only a piece of muslin over 
the mouth of the bottle to exclude dust. These tablets were assayed 
in November, 1913, by the modified Scoville method after having 
been stored as stated above for six years with the following results : 

Tablets in stoppered bottle 0.0130 grain 

Tablets in unstoppered bottle 0.0040 grain 

" In all probability these tablets would not have assayed, by the 
modified Scoville method, much over 0.015 grain when made. (Com- 
pare assay tablets in first experiment April 12, 19 12.) 

What Is Soap? 

Certain resolutions passed at a recent meeting of the Ohio State 
Pharmaceutical Association regarding the description of soap cer- 



Current Literature. 



( Am. Jour. Pharm. 
\ April, 1914. 



tainly need to be accepted with a considerable amount of reservation. 
Copies of the resolutions passed at the meeting were furnished to the 
State Authorities of the Federal Department of Agriculture and the 
Revision Committee of the United States Pharmacopoeia and 
National Formulary. 

The following were the actual resolutions adopted : 

" Whereas, The market is flooded with various mongrel soaps, 
masquerading as Castile Soap ; and 

" Whereas, The Designation Castile Soap has long been recog- 
nized as and held to refer to U. S. P. Soap ; therefore be it 

" Resolved, That we recommend the adoption of such State and 
National Standards as will forbid the use of the term ' Castile ' as 
applied to any soap other than the U. S. P. Soap ; and be it further 

" Resolved, That we recommend the incorporation of the term 
Castile Soap as a synonym for Sapo in the forthcoming Pharma- 
copoeia ; and be it further 

" Resolved, That copies of these resolutions be furnished to & 
State Authorities, the Federal Department of Agriculture, and th: 
Revision Committee of the U. S. P. and N. F." 

Now we question very much whether the description " Castile 
Soap " is one that should be maintained at all, and in connection at 
any rate with British pharmacy it should not be forgotten that the 
name " Castile Soap " as a synonym for hard soap was abandoned 
in the British Pharmacopoeia of 1898, although it was official in the 
Pharmacopoeia of 1885. 

The hard soaps of various Pharmacopoeias are described in a 
variety of ways, and in one case only does the title indicate that the 
source should be Spanish, namely, the Russian Pharmacopoeia, which 
describes hard soap as Sapo Hispanicus Albus. 

The following are the titles employed in the various Pharma- 
copoeias, and we see no reason why the British Pharmacopoeia title 
should not be one generally adopted : 

In the United States Pharmacopoeia simply Sapo ; Belgian 
Pharmacopoeia, Sapo Officinalis ; Danish and Dutch, Sapo Medicatus ; 
Hungarian, Sapo Venetus ; Norwegian, Sapo Albus Oleaceus ; 
Spanish, Jabon de Sosa ; Swedish, Sapo Medicatus ; Swiss, Sapo 
Oleaceus. 

It is a pity that in certain works of reference, notwithstanding 
that the synonym Castile Soap has been officially dropped, the soap 
should be so described or referred to. For example, in Squire's Com- 



Am. Jour. Pharm. > 
April, 1914. / 



Current Literature. 



panion to the British Pharmacopoeia, edition 1908, under the solu- 
bility test, reference is made to the digestion of 30 grs. of white 
Castile Soap in 1 oz. of cold alcohol 90 per cent., when only 24 grs. 
were dissolved, whilst in the recently published Codex, under Hard 
Soap, the description is " Hard or Castile Soap," thus assuming that 
Castile Soap is a synonym for hard soap. It is well recognized in 
commerce that the soap now supplied as Castile Soap is prepared 
from a variety of other oils than olive oil. 

The resolutions, therefore, that have been adopted by the Ohio 
Pharmaceutical Association must, in the light of commerce of to- 
day, be vieweci with some considerable amount of reserve. Editorial 
in "Perfumery and Essential Oil Record/' September, 191 3. 

Pharmaceutical Education. — Dr. H. Thorns writes in a very 
informative and comprehensive manner on the question of prelim- 
inary educational requirements and pharmaceutical training in Ger- 
many and other European countries. It is worthy of note that he 
lays particular stress on the value to a student of a good prelimi- 
nary education. If he possesses that valuable asset, an asset that is 
the foundation of success in any calling, he will, other things being 
equal, be able to overcome what would otherwise seem insurmount- 
able obstacles with ease and facility. It is proverbial that in building 
operations the stability of the superstructure depends upon a well- 
laid foundation. So with pharmacy or any of the learned pro- 
fessions. 

It is also worthy of observation that the general trend of exami- 
nations in determining a candidate's fitness to practise his calling 
is toward practical laboratory work. Written and oral examina- 
tions, combined with practical laboratory work, are the order of the 
day in Germany as well as in most other European lands. This 
desirable condition has obtained in Germany for many years, as 
has likewise the necessity of students possessing a good general 
education for entrance to the study of a profession. 

It does not require a great intellect to see and appreciate the 
value of further educational development along these lines. It 
means so much to the general welfare of a community from the 
stand-point of safeguarding the public health. Men of Thoms's 
type, both here and abroad, are emphasizing this more and more 
every day. 

Not only is the pharmacist expected, nay, legally required, to 
stand between the physician and the patient, but he must be able, 



190 Current Literature. { Am Apdi r 'i9i4 arm " 

in these days when he (the pharmacist) depends to such a large 
extent upon the manufacturing pharmacist for his pills, tablets, solu- 
tions in ampules, tinctures, and extracts both solid and fluid, and other 
pharmaceuticals, to stand as a bulwark of protection between the 
manufacturer and the consumer. In other words, the pharmacist 
is responsible for the purity and accuracy of dosage of all medicines 
dispensed, whether made by himself or a manufacturing house. 

And in order to accept and shoulder this responsibility he must 
be thoroughly grounded in the principles of the allied branches 
which comprise the science and art of pharmacy. He must be 
familiar with and capable of using modern methods and apparatus 
for the investigation of chemicals and galenical preparations ; he 
must be able to make analyses, both of inorganic and organic chem- 
icals; he also should be able to make microscopical examinations 
of sections of vegetable drugs and powdered drugs; in short, he 
should be a pharmacognist ; he should be thoroughly conversant 
with the underlying principles governing bacteriology, as the use of 
sterile solutions and preparations by physicians is becoming more 
prevalent every day and it is logical that the pharmacist should be 
looked to as a source to supply this demand. 

Thorns makes it perfectly clear.that this development of pharmacy 
along lines of greater scientific efficiency is not by any means Uto- 
pian ; that there is great need of better efficiency among the rank 
and file of the profession, and that it is quite possible and practicable 
for the student of today to receive the necessary training for the 
realization of this object. If pharmacy is to continue to exist on 
a scientific basis its proper development must be along a rigorous 
scientific curriculum. — Arbeiten aus dem Pharmaseutischen, Institut 
der Universitat, Berlin, vol. x, page 189, 191 2. 

John K. Thum. 

Radium and Radium Salts. 1 

Radium is a bivalent metallic element closely related to barium. 
It is exceedingly reactive, making it difficult to isolate in its metallic 
state and after isolation to keep in a pure state, as it reacts with air, 
forming the oxide, nitrite and finally the carbonate. On account of 
this activity it is only produced in the form of its salts, principally 
as the bromide, chloride, sulphate and carbonate. 



1 Jour. Amer. Med. Assoc., January 3, 1914, p. 41. 



Am. Jour. Pliarm. ) 
April, 1914. } 



Current Literature. 



191 



The most important property of radium is its radio-activity upon 
which depends its therapeutic value. Radio-activity is defined as 
" the property of spontaneously emitting radiations capable of pass- 
ing through plates of metal and other substances opaque to ordinary 
light and having the power of discharging electrified bodies." A 
spontaneous disintegration of the atoms characterizes all the radio- 
active elements and it is in this transmutation or splitting of the 
atom that the rays are shot out, some being material in nature, others 
electrical or of the nature of light. This spontaneous transmutation 
of radium is going on at a regular rate, which is independent of the 
state of combination of radium in the molecule of its compounds. 

To determine the radio-active value of radium, use is made of its 
property of ionizing gases. Thus when radium is allowed to act on 
the air in a charged gold-leaf electroscope the air becomes ionized 
and therefore a conductor of electricity and allows the charge to 
leak out, causing the leaf in the electroscope to move. By observing 
the rate of movement of the leaf in a calibrated apparatus the radio- 
activity can be determined. 

Quantities and concentrations of radium emanation are expressed 
in terms of " curies " and Mache units. A " curie " is the amount 
of emanation in equilibrium with 1 gram of radium; a microcurie, 
one millionth of a " curie," is the amount of emanation in equilibrium 
with 0.001 mg. radium and is equivalent to about 2,500 Mache units. 

Relation of Radium, -Radium Emanation and Rays. — The rays 
are largely derived indirectly from radium through the formation 
of its " active deposit," according to the following scheme : 

aparticle 

/ 

Rad. aparticle 

\ / 

eman. 

\ 

ac. dep. sh^t: Rays. 

These rays are divided into three groups, the alpha, beta and 
gamma, which differ in their velocity and penetrative power. The 
alpha and beta rays consist of minute particles of matter electrically 
charged and moving with a velocity almost equal to that of light. 
They are for the most part of relatively feeble penetrating power. 
The gamma rays are vibrations in the ether, very similar to X-rays, 
and of high penetrating power. Therapeutically the last group is 
the most useful. 

Radium emanation is continuously given off from aqueous solu- 



192 



Current Literature. 



(Am, Jour. Pharm. 
\ April, 1914. 



tions of radium salts. It can be collected as it escapes from the 
solution, drawn off through the use of the mercury pump, or by 
other suitable means, quantitatively determined by either the alpha 
or gamma ray electroscope, brought into solution in water for in- 
ternal or external use or be set free in an emanatorium for inhalation 
treatment. It may be collected into small glass containers and this 
used in place of the applicators described under surgical use. 

Actions and Uses: Radium emanation is said to increase the 
excretion of uric acid in the urine and to decrease its concentration 
in the blood ; to increase somewhat the number of red blood-cor- 
puscles ; to cause temporary leukocytosis early in the course of 
treatment, the mononuclear increase being relatively greater ; to lead 
frequently through long-continued use to leukopenia, although no 
appreciable benefit is observed in leukemia. It is said that radium 
increases general metabolism, and in vitro activates certain enzymes, 
pepsin, pancreatin, rennin, autolytic ferments, tyrosinase and dias- 
tase. 

It has been claimed that radium emanation is of value in all 
forms of non-suppurative, acute, subacute and chronic arthritis 
(luetic and tuberculous excepted), in chronic muscle and joint rheu- 
matism (so-called), in arthritis deformans, in acute and chronic 
gout, in neuralgia, sciatica, lumbago, and in tabes dorsalis for the 
relief of lancinating pains. Its chief value is in the relief of pain. 

Surgical Use: The efficiency of the treatment is due to the beta 
and gamma rays. The quantity of ray is proportional to the amount 
of radium element represented in the salt or the emanation. Pure 
gamma rays may be employed when the apparatus is surrounded by 
at least 3 mm. of lead. Nearly all pathologic tissues are more sensi- 
tive than normal tissues. There is, however, a wide variation in 
the normal tissues ; e.g., the ovary and the sexual organs are very 
sensitive, the eye and nervous tissues very unsensitive. In skin dis- 
eases marked results are obtained with epitheliomata, birthmarks 
and scars. 

Technic: Usually heavy doses with epitheliomata, light doses 
with other conditions. New growths, benign and malignant, of the 
pelvic organs, the breast, the neck and other parts of the body 
have been most favorably influenced in some cases. The growths of 
the mucous membrane of the mouth are quite resistant. There is a 
remarkable sedative effect in true neuralgia, as well as those due to 
tumor pressure. The dosage for internal work is heavy, " hundreds 
of milligrams," and always with the pure gamma rays. The technic 



Am. Jour. Pharm. ) 
|April, 1914. J 



Current Literature. 



193 



of filtration, of length of application and of amount is still in an 
experimental stage. 

The radium salts and the emanation can be placed in any sealed 
container, but preferably in glass. 

Dosage: It may be administered as baths, by subcutaneous in- 
jection in the neighborhood of an involved joint (0.25 to 0.5 micro- 
curie in 1 or 2 c.c. distilled water), by local application as com- 
presses (5-10 microcuries), by mouth as a drink cure (in increas- 
ing doses of from 1-10 to 10 microcuries three or more times a day), 
by inhalation, the patient for two hours daily remaining in the 
emanatorium, which contains 0.0025 to 0.25 (average 0.1) micro- 
curie per liter of air. 

Radium Chloride. 

Radium chloride is the anhydrous radium salt, RaCl 2 , of hydro- 
chloric acid. While nearly pure radium chloride, containing 76.1 per 
cent, radium (Ra), is said to be obtainable, the market supply is a 
mixture of radium chloride and barium chloride and is sold on the 
basis of its radium content. 

Actions and Uses: See Radium. 

Dosage: See Radium. 

Non-Proprietary Preparation : 

Radium Chloride, Standard Chemical Co. — Radium chloride is 
supplied in the form of a mixture of radium chloride and barium 
chloride for use in radium baths, radium drinking-water and inhala- 
toriums. It is sold on the basis of its radium content. 

Manufactured by the Standard Chemical Co., Pittsburgh, Pa. 
(The Radium Chemical Co., Pittsburgh, Pa.). 

Pure anhydrous radium chloride occurs as a white or slightly 
brownish crystalline substance, soluble in water. 

The presence of radium can qualitatively be demonstrated by 
electroscopic or by photographic methods. 

The quantitative determination of radium is carried out accord- 
ing to the method of Rutherford and Boltwood (Rutherford's 
" Radioactive Substances and their Radiations "). 

Radium Sulphate. 

Radium sulphate is the anhydrous radium salt, RaS0 4 , of sul- 
phuric acid. While nearly pure radium sulphate, containing 70.2 
per cent. (Ra), is said to be obtainable, the market supply is a 



194 



Current Literature. 



{Am. Jour. Pharni. 
u April, 1914. , 



mixture of radium sulphate and barium sulphate and is sold on the 
basis of its radium content. 

Actions and Uses: See Radium. 

Dosage: See Radium. 

Non-Proprietary Preparation : 

Radium Sulphate, Standard Chemical Co. — Radium sulphate sup- 
plied in the form of a mixture of radium sulphate and barium sul- 
phate for use in applicators. It is sold on the basis of its radium 
content. 

Manufactured by the Standard Chemical Co., Pittsburgh, Pa. 
(The Radium Chemical Co., Pittsburgh, Pa.). 

Pure radium sulphate occurs as a white substance insoluble in 
water and dilute acids. 

The presence of radium may be qualitatively determined by 
electroscopic or by photographic means. 

The radium content may be determined as in the case of radium 
chloride. 

Warning to Users of Turpentine for Medicinal or 
Veterinary Purposes. 

As the result of an investigation by the U. S. Department of 
Agriculture, it has been found that the adulteration of turpentine 
with mineral oils is so widespread that druggists and manufacturers 
of pharmaceutical products and grocers' sundries should exercise 
special caution in purchasing turpentine. Those who use turpentine 
for medicinal and veterinary purposes, unless they are careful, 
run the risk of obtaining an adulterated article and unnecessarily 
laying themselves open to prosecution under the Food and Drugs 
Act. 

It has been found, moreover, that the turpentine sold to the 
country stores especially, as usually put out by dealers and manu- 
facturers of grocers' sundries, is often short in volume by as much 
as 5 or i o per cent. Dealers, therefore, should also protect them- 
selves through a guarantee from the wholesaler that the bottle con- 
tains the full declared volume. 

The Department has found that turpentine may be adulterated 
in the South where it is made and that the further it gets from the 
South the more extensively and heavily it is adulterated. 

In all cases, druggists, manufacturers and wholesale grocers 
should satisfy themselves that the turpentine is free from adultera- 
tion and is true to marked volume. 



THE AMEEICAN 



JOU 




OF PHARMACY 



NOTES ON 



ATION OF NITROGLYCERINE. 



By F. W. Heyl and J. F. Staley. 



After abandoning the older nitrometer method for the control 
of nitroglycerine in pharmaceutical preparations, it was the practice 
in this laboratory during a considerable period to use in its place 
the modified Kjeldahl method wherever possible. The Kjeldahl 
method was found to give results in this instance fully as reliable as 
in the case of other highly nitrated organic substances such as 
picrates and picrolonates, which have thus been successfully 
analyzed. 

Recently the latter method has been supplanted in this laboratory 
by that introduced by Scoville, 1 particularly when preparations bear- 
ing minute quantities are under examination. Before abandoning 
the Kjeldahl method for the superior method of Scoville, we first 
compared the results obtained by using these two methods in the 
routine analysis, upon various samples of nitroglycerine prepara- 
tions. In view of the comparatively large number of collaborators 
who took part in the cooperative work recently described 2 in the 
annual report of the Official Agricultural Chemists, the results here 
given may be of some interest. 

In this valuable bulletin the nitroglycerine found by the modified 
Scoville method is compared with results obtained gravimetrically 
upon the same sample by extracting with anhydrous ether. It was 
the experience of some of the collaborators that the gravimetric 

1 Amer. Jour. Pharm., 83, 359, 1911. 

2 Bureau Chemistry U. S. Dept. Agric. Bull., 162, 214, 1912. 



(195) 



196 Notes on Estimation of Nitroglycerine. { Al \fy U r i»ul arm ' 

determination of nitroglycerine was inaccurate, and this would be 
even more liable to error in anything but the simplest preparations. 
It is, therefore, of interest to note the comparisons here given of 
nitroglycerine content as determined by the Scoville method and by 
the modified Kjeldahl. 

Scoville 3 has already briefly compared these values and the 
figures here given lead to the same conclusions as his, i.e., that the 
results obtained by these methods are quite alike, and that .the varia- 
tions are due to the difficulties of the methods. 

For the analysis of tablets containing minute quantities there 
can be little doubt that the colorimetric method is both the easier 
and the more accurate. But in the case of the stock preparations 
such as the concentrated alcoholic solutions and triturations, the 
larger quantities of nitroglycerine under analysis make it possible 
to obtain closely agreeing results by the modified Kjeldahl method. 
The manufacturing processes can be closely controlled when the 
stock substances are standardized by the Kjeldahl and the finished 
product by the colorimetric method, particularly when the condi- 
tions are so standardized that a definitely known loss of nitro- 
glycerine, previously determined, is allowed for. Such data are 
given in the table. 

It will be observed, that under the conditions employed for man- 
ufacture, the losses of nitroglycerine involved have been reduced to 
quite narrow limits, averaging about five per cent for moulded 
tablets and about eleven per cent for compressed ones. Our find- 
ings on the compressed tablets "are at variance with the losses pre- 
viously recorded 4 ; but this is due to the fact that the tablets are pre- 
pared by mixing dry granulations instead of attempting to granulate 
the mixture. A tablet prepared in this way neither discolors nor 
loses its strength, and there is no doubt but that a stable standard 
product results, at least as long as the preparation is properly pre- 
served. 

Experimental. 

For the colorimetric analyses a method equivalent to that out- 
lined in the report 5 of the Official Agricultural Chemists was em- 
ployed. 



3 Lor. cit. 

4 Amee. Jour. Pharm., 79, 555, 1907. 

5 hoc. cit. 



Am '£y r 'lS 11 ™' } Notes on Estimation of Nitroglycerine. 197 

The nitrogen determinations were made as follows : Approxi- 
mately one gram of the ten per cent alcoholic solution was used for 
analysis. Where tablets and triturations were analyzed they were 
first extracted with anhydrous ether, and the ether extracts were 
evaporated to dryness under reduced pressure at room temperature. 
The residue was taken up in 1 to 2 c.c. alcohol and collected at the 
bottom of the flask. Upon this alcoholic solution one gram of 
salicylic acid was placed and then the Kjeldahl flask was cooled in a 
freezing mixture. Upon this 40 c.c. of the customary salicylic acid 
in sulphuric acid solution (previously chilled) was poured and then 
the mixture was allowed to warm to room temperature, with occa- 
sional agitation. The nitration mixture was reduced by the gradual 
addition of 2 grams of zinc dust, and then the reduction was com- 
pleted by allowing the reaction to continue for six hours. The 
mixture was heated gently for five minutes, ten grams of potassium 
sulphate was added, and the Kjeldahl determination was then finished 
in the usual manner, using N/20 solutions. 

The following table gives the results of analyses on tablets, some 
prepared experimentally and some commercially: 



Preparation analyzed. 



r. Nitroglycerine sol. . 

2. Nitroglycerine trit. 

3. Compressed tablets 

4. Compressed tablets 

5. Compressed tablets 

6. Compressed tablets 

7. Compressed tablets 

8. Moulded tablets. . . 

9. Moulded tablets. . . 
10. Moulded tablets. . . 

EX. Moulded tablets. . . 

12. Moulded tablets. . . 



Nitroglycerine 

calculated 
gm. per tablet. 



0. 0007744 

0. 0005194 

0. 0007732 

0. 0006234 

o. 0004015 

0. 0006493 

0. 000658 
,0. 00053S1 

0. 000720 
0. 000688 



Found 
Kjeldahl. 



9.83% 
9.65% 
9.66% 
9.82% 
9.56% 
-9.7i% 
9-99% 
9.63% 
0007228 
0007039 



0.0004557 
o. 0004768 
o. 0004546 
0.0007395 



o. 0005298 
o. 0005298 

0. 0003512 
o. 0003474 
o. 0006328 
o. 0006328 
o. 0006280 
0.0005237 



0. 000629 



Found 

Scoville. per 



9.75% 
9-87% 



10.03% 
9-88% 



0. 0007044 
0. 0006843 
o. 0007083 
0. 0004540 
0. 0004508 

o. 0007038 
0. 0006967 
0. 0006850 
0.0005273 
0.0005559 

0.0005559 
o. 0003552 
o. 0003596 
o. 0006588 

0. 000616* 
o. 0005085 
o. 0005184 
0. 0006836 
o. 0006480 



* This analysis was made three months after the Kjeldahl. 



198 Use of Antitoxins and Vaccines. { Xm w™\$u &rrn ' 

Since the losses involved in the manufacture of these products 
must vary with the mechanical details, a brief description of the 
mechanical conditions employed will suffice. The compressed tablets 
were usually made in unit runs of 50,000 and the calculated strength 
in the table was found by taking into account both the waste, which 
was in each case weighed, and also the over or under run in number. 
The moulded tablets were made in unit batches of 15,000 and dried 
artificially in 45 to 60 minutes. All the calculations of loss are based 
on the colorimetric determinations. 
Contribution from the Chemical Research 

Laboratory of The Upjohn Company. 
Kalamazoo, Mich., March, 1914. 



THEORIES UNDERLYING THE USE OF ANTITOXINS 
AND VACCINES.* 
By A. Parker Hitchens, M.D., Glenolden, Pa. 

The action of antitoxins has so definitely passed beyond the 
stage of pure speculation that I think there will be little difficulty in 
expounding the theories underlying their use. With regard to 
vaccines likewise we have come to understand more clearly their 
mode of action without the use of a terminology recognized only by 
the initiated few. 

Out of studies in immunology — the science dealing with the 
mechanism of contagious diseasea — have developed methods by 
which the body may be assisted either to prevent disease-producing 
germs from gaining a foothold, or to eliminate them after they 
have become established. • 

The disease-producing bacteria are classified in various ways, 
according to their functions. For our present purpose, the classifica- 
tion of most interest is that which considers the bacteria according 
to their manner of causing disease. Thus we find that one group 
of bacteria produces definite, soluble, and diffusible poisons, and 
that all the symptoms of the disease are directly or indirectly de- 
pendent on the action of these poisons upon the tissues for which 
they have an affinity. The second group of bacteria, on the con- 
trary, does not produce soluble and diffusible toxins in appreciable 

* Read at a meeting of the American Pharmaceutical Association, Phila- 
delphia Branch, April 7, 1914. 



Ana M J a°y Ur iyi4 arm '} ^ sc °f Antitoxins and Vaccines. 199 

quantity — their effect is brought about by a much more complicated 
process. We believe the production of disease by this class of 
bacteria is not a function in which they alone participate, but is the 
result of their interaction with the body cells. 

Antitoxins. 

Belonging to the first class of bacteria, the only organisms of 
interest to us are the diphtheria bacillus and the tetanus bacillus. 
These produce soluble and diffusible poisons — toxins; and spon- 
taneous recovery from these diseases depends upon the generation 
by the tissues of a substance which will neutralize the toxins — 
antitoxins. The requisite antitoxins can be easily produced in 
animals and transferred to the bodies of patients by administering 
the blood serum of the treated animals. 

For obvious reasons, horses are generally selected for the pro- 
duction of antitoxin. The germs in question are developed upon a 
fluid artificial culture medium — veal broth. After the bacteria are 
removed from the full-grown culture, the sterile filtrate, containing 
the specific toxins, is injected subcutaneously into the horses. The 
horses react by the production of antitoxin. Enormous quantities 
of toxin are administered, and consequently enormous quantities of 
antitoxin are generated and stored in the blood serum of the 
animal. The antitoxins on the market, then, consist of this blood 
serum, either native or chemically treated so that the pseudoglobulin 
constituent of horse serum which carries with it the antitoxic 
principle is removed and furnished, in solution, in as pure a state 
as possible. 

The strength of the antitoxin is determined by titrating it against 
toxin, the guinea pig being used as indicator. In defining a unit at 
present, there is no more reason to say that it is the amount that 
will neutralize 200 fatal guinea-pig doses of a theoretically pure 
toxin than there is, in defining an inch, to say that it has a definite 
relation to the circumference of the earth. Twelve inches make 1 
foot, 36 inches 1 yard ; 1000 units of diphtheria antitoxin constitute 
the immunizing dose, 5000 units the average initial curative dose ; 
1500 units is the official immunizing dose of tetanus antitoxin. 

The action of diphtheria antitoxin may be clearly illustrated 
by imagining the disease to be due to a mineral acid generated 
within the body and poured into the circulation in constantly in- 
creasing quantities. According to the urgency of the case, let us 



200 Use of Antitoxins and Vaccines. j Am • M J a ° y ur * 19 i^ arm ' 

inject a corresponding quantity of a harmless alkali. The acid is 
neutralized, the disease is controlled, and the fate of the patient 
now depends only upon the amount of damage done to the tissues 
before the alkali was administered. 

In tetanus the case is slightly different. Tetanus toxin has a 
strong affinity for the nerve tissues, and the compound formed by 
this union cannot be split up by antitoxin. After symptoms of the 
disease have developed, there is but one hope in treating tetanus 
with antitoxin. If treatment has begun before the lethal quantity 
of toxin has been fixed by the nervous tissue, and if the amount of 
antitoxin then administered be sufficient to neutralize the free toxin 
in the blood, there is a chance that recovery may ensue. 

Bacterial Vaccines. 

For a clear understanding of the action of bacterial vaccines, 
it may be helpful to consider this subject from the standpoint of 
our knowledge of anaphylaxis. Anaphylaxis, in its derivation, 
means a lack of resistance — it is the opposite of prophylaxis. Richet, 
in his investigation of certain poisons derived from sea urchins, 
noted that an injection of this poison into a dog, instead of render- 
ing the animal immune to a second dose, actually made him more 
susceptible. The work of Rosenau and Anderson showed still more 
clearly the operation of this phenomenon. 

Anaphylaxis concerns the effect of proteins or albuminous sub- 
stances upon animals ; it concerns all proteins, whether they are 
poisonous in themselves or not ; for instance, egg white and normal 
horse serum act precisely as the proteins of the plague bacillus or 
of the typhoid bacillus. And, furthermore, the proteins of dead 
bacteria act practically in the same way as the proteins of living 
bacteria. It must be remembered, however, that anaphylactic 
symptoms can be produced only by proteins foreign to the animal ; 
that is, anaphylaxis cannot occur in a guinea pig from the repeated 
injection of guinea-pig serum, nor can the symptoms be produced 
in a horse by the injection of horse serum. 

If we inject a guinea pig parenterally — that is, by any route 
except by the gastro-intestinal canal — it does not appear to suffer 
the slightest inconvenience. If, however, we inject this animal, two 
or more weeks later, with the same protein, it will die within one 
or two minutes and with very definite symptoms accompanying 
death. This is a manifestation of anaphylaxis. 



Am 'M^ r i9i4 arm ' } Use of Antitoxins and Vaccines. 201 

For an explanation of this phenomenon we must go back to the 
work of Prof. Victor C. Vaughan upon the chemistry of the 
protein molecule. Vaughan has shown that a protein, treated 
chemically according to his method, is split into two parts — the one 
poisonous, the other non-poisonous. The poisonous part obtained 
from all proteins is the same whether it results from the splitting 
of egg white or from the splitting of typhoid bacilli; the symptoms 
leading to death in the guinea pig are identical. This poisonous 
part, then, is a poison and has no other function or effect ; one dose 
has no bearing upon the effect of a subsequent dose, no hyper- 
susceptibility is produced, and no tolerance, even by repeated 
administration. 

The non-poisonous part, on the other hand, is specific in its 
action. The non-poisonous part of typhoid bacillus protein will 
immunize an animal against typhoid infection, but not against 
infection with colon bacilli ; the non-poisonous part of horse serum 
will sensitize a guinea pig to horse serum, but not to goat or 
sheep serum. 

These results of Vaughan's work upon the chemistry of proteins 
suggest an explanation of the mechanism of anaphylaxis ; they show 
us that, instead of being the opposite of immunity, anaphylaxis is 
merely one of its manifestations ; and, furthermore, they give us a 
clearer understanding of immunity itself. 

When foreign proteins are injected into the tissues of an animal, 
the body cells at once set to work to remove this protein. They 
prepare a ferment capable of splitting the protein molecule, which 
possibly because of its size is not diffusible, into smaller fractions 
able to pass into the circulatory system and be thence eliminated. 
These fractions of the protein molecule are similar to those ob- 
tained by Vaughan in his chemical splitting; that is, a poisonous 
part which, after the first injection, is liberated slowly and is there- 
fore harmless in its effect, and a non-poisonous specific part which 
stimulates the body cells to produce a specific ferment-like sub- 
stance. About two weeks after injection the protein has been 
entirely removed from the tissues, the poisonous part has been 
eliminated so gradually that no symptoms have resulted, and the 
non-poisonous part has stimulated the tissues to generate a large 
amount of specific protein-splitting ferment. 

At this point we must pause to note that, according to Vaughan, 
the protein-splitting ferment includes the antibodies so difficult to 



202 



Use of Antitoxins and Vaccines. 



Am. Jour. Pharm. 
May, 1914. 



understand in the theories of the German and French schools of 
immunity. This theory of the American school does' not contradict 
the fact established by Metchnikoff, and further elucidated by 
Wright, that the white blood-corpuscles play an active part in 
the removal of foreign proteins, whether they be cells or fluids; 
nor is it out of harmony with the theory of Ehrlich, who 
gives to the group of antibodies — collectively called " the ferment " 
by Vaughan — different names according to their functions. 

The guinea pig, then, at the end of two weeks after the first 
injection of, let us say, horse serum contains in his tissues no trace 
of horse serum ; but he does have within his body a large quantity 
of protein-splitting ferment which may remain in the tissues for a 
long time ; and, even if it disappears, the power to generate this 
ferment upon demand may remain permanently. If we now inject 
into this guinea pig a second dose of horse serum, the proteins 
contained therein are at once attacked by the specific ferment ; 
digestion occurs almost immediately, resulting in the liberation 
of a large quantity of the poisonous part of the protein molecule ; 
the animal is overwhelmed by it and dies usually in less than five 
minutes. A dose sufficiently large to cause death depends upon the 
method of injection; if injected into the circulation or into the 
brain, 1/20 ex. is sufficient; if injected subcutaneously, however, at 
least 5 c.c. is usually necessary. 

Now as to the bearing of this" phenomenon upon infectious 
disease — Vaughan has used typhoid fever as a typical illustration. 
Infection results from the entrance of a few typhoid bacilli into 
the tissues under circumstances which permit their growth and 
multiplication. There is normally present in the body a small 
amount of a non-specific protein-splitting ferment which attacks 
the typhoid bacilli, liberating the non-poisonous part, which in turn 
begins to stimulate the tissues to the production of a specific anti- 
typhoid ferment. We know that in guinea pigs it takes from eight 
to fourteen days to produce enough ferment to cause serious 
symptoms of intoxication upon the injection of a second dose of the 
protein. Now this period corresponds exactly to the incubation 
period in typhoid fever. It is during this time that the typhoid 
protein-splitting ferment is produced in increasing quantities, while 
the typhoid bacilli are rapidly growing in numbers. The ferment 
sets free the poisonous part in gradually increasing quantities with 
the final appearance and progressive increase of fever and the other 



Am 'May r 'iw4 arm '} ^ se °f Antitoxins and Vaccines. 203 

symptoms of the disease. This process continues up to the point 
where the number of typhoid .bacilli destroyed each day equals the 
number reproduced in the lesion. This balance is maintained for a 
time until the number of bacilli destroyed exceeds those reproduced. 

A patient recovered from typhoid fever has remaining in his 
tissues a large amount of typhoid protein-splitting ferment, so that 
when typhoid bacilli again gain entrance to his tissues they are at 
once attacked and destroyed before they have a chance to develop. 
Obviously there is no intoxication, because the amount of typhoid 
proteins is infinitesimal compared to the amount necessary to result 
in anaphylactic shock. 

It is now easy to understand the action of typhoid vaccine. 
When we inject beneath the skin a number of typhoid bacilli, their 
disintegration is started by the normal proteolytic ferments in the 
body. A second and third dose given at intervals of about ten days 
increases the quantity of specific typhoid protein-splitting ferment. 
The theory of typhoid immunity by means of bacterial vaccines 
applies equally to the production of immunity to other infecting 
bacteria. The theory underlying the use of bacterial vaccines in 
disease is based on the fact that the tissues affected are unable to 
produce a sufficient quantity of the specific ferment to overcome 
the infection. The injection of bacterial proteins in a healthy part 
of the body leads to the production there of these antibodies, which 
are conveyed to the focus of infection through the circulatory system 
and thus assist the local cells. 

It will now be clear that the requisites to success in vaccine 
therapy are (1) that the vaccine injected must contain bacterial 
proteins identical in kind with those causing the infection, (2) 
that the ferment produced locally must come in contact with the 
infecting bacteria. For one with proper training it is not hard 
to determine the kind of bacteria causing an infection ; nor is it hard 
to obtain either a stock vaccine representing these bacteria or to 
prepare an autogenous vaccine identical with them ; and it is a 
very simple matter to inject these bacterial suspensions beneath 
the skin of the patient. 

If the patient is not in the last stages of disease, there is not one 
chance in many thousands that his tissues will fail to produce the 
proper antibodies or ferments. If the patient shows no improve- 
ment as result of the treatment, it behooves the physician to use 
means by which the ferments may be induced to perform their 
function. 



204 Use of Antitoxins and Vaccines. { Am "Ma°y r 'i9u arm " 

In some infections, as in staphylococcic infection, accessory 
measures are seldom needed, while in streptococcic infections they 
are nearly always necessary. In gonococcic infections of the urethra 
and prostate, the mere injection of vaccines accomplishes but little; 
in gonococcic infections of the joints, however, the vaccine is 
apparently sufficient. 

We are indebted to Besredka of the Pasteur Institute in Paris 
for an improvement upon bacterial vaccines which constitutes a 
real advance in vaccine therapy. As said above, when the bacterial 
vaccine is injected beneath the skin a small quantity of the protein 
is split up by natural ferments and the specific non-poisonous part 
thus liberated stimulates the production of ferments which con- 
tinue the disintegration until the maximum effect of the vaccine 
is obtained. 

The ferment itself is composed of at least two constituents; one 
is specific, and by Ehrlich has been called amboceptor (the opsonin 
of Wright is a similar antibody). This substance has the power 
of fixing itself to the bacteria, thus preparing them for digestion 
by another substance which is not specific but is always present 
in the blood of healthy animals, and because the latter completes 
the ferment action it is called complement. Besredka proposed 
that amboceptor be utilized to prepare the bacteria for the immediate 
action of the complement. The amboceptor is obtained by injecting 
goats or sheep with massive doses of bacteria like those it is desired 
to sensitize. Bacteria thus prepared for the action of the com- 
plement were said to be " sensitized," and the suspensions of such 
bacteria were called by him " sensitized vaccines." The advantage 
they have over ordinary bacterial suspensions is that they eliminate 
the period during which the specific ferment is being formed. 
" Sensitized vaccines " have already been used extensively in France 
and also to a certain extent in England. The published reports 
amply attest their superiority. 



Antibacterial Serums. 



The so-called " therapeutic or antibacterial serums " include 
antistreptococcic, antipneumococcic, and antimeningococcic serums. 
These are prepared by the injection of horses first with dead and 
then with living bacteria. In the case of antimeningococcic serum 
injections of autolyzed bacteria are alternated with the cocci them- 



^ May r i9i4 arm * } Use °f Antitoxins and Vaccines. 205 

selves. The autolysate contains a toxic substance which causes 
the production of some antitoxin. This serum, like antidysenteric 
serum, partakes, therefore, of the nature of both an antitoxic and 
an antibacterial serum. 

These serums depend for their activity upon substances called 
ferments by Vaughan, but, according to the nomenclature of Ehrlich, 
" antibodies " ; that is, substances antagonistic to the bacteria. Used 
in sufficiently large doses, antibacterial serums have undoubtedly 
great value. The chief difficulty lies in the fact that no method 
has so far been found by which antibacterial serums can be pro- 
duced comparable in potency with diphtheria antitoxin. 

It is well known that a much larger dose of any curative serum 
must be used if it is injected subcutaneously than if injected intra- 
venously. Realizing this fact and the relative weakness of anti- 
bacterial serums, there is but little doubt that their use intravenously 
will be resorted to in the future with increasing frequency. 

Summary. 

1. There are two classes of bacteria with regard to their method 
of producing disease: (a) Those that produce soluble and diffusible 
toxins, and (b) those that do not. 

2. The toxin-producing bacteria are the diphtheria bacillus and 
the tetanus bacillus. 

3. Antitoxins produced by injecting horses with the specific 
toxins are antagonistic to the specific toxic products of the bacilli 
in a manner very similar to the antagonism between acid and alkali. 

4. To the second class belong the great majority of the disease- 
producing bacteria. 

5. The symptoms in the diseases caused by the latter are prob- 
ably the result of the action of their specific metabolic products 
combined with the effect of the liberated poisonous part of their 
protein molecule. 

6. Recovery from such infectious diseases depends upon the 
production of sufficient specific protein-splitting ferment to remove 
their causative bacteria from the tissues. 

7. The amount of this specific protein-splitting ferment may be 
increased by injecting bacteria of the same kind beneath the healthy 
skin. 

8. Immunity from infectious disease depends upon the existence 



2C>6 



Autogenous Vaccines. 



Am. Jour. Pharm, 
May, 19U. 



in the tissues of sufficient specific protein-splitting ferment to dis- 
solve invading bacteria before they have a chance to develop. 

9. The rational administration of bacterial vaccines presupposes 
accurate diagnosis and the administration of bacteria identical in 
kind with those causing the infection. It depends, furthermore, 
upon the ability of ferments and antibodies to come in contact with 
the infecting bacteria. 

10. " Sensitized vaccines " are superior to ordinary vaccines 
because they reduce the preliminary period during which the in- 
jected bacteria are being split up so that the non-poisonous part may 
be available for the production of specific antibodies. 

11. Antibacterial serums — antistreptococcic and antipneumo- 
coccic — depend for their activity upon their content in specific anti- 
bodies or ferments. 

12. The amount of these ferments in even the best serums is 
relatively small, and the serums must therefore be used in larger 
doses than has been customary in the past. 

13. Antimeningococcic serum is both antibacterial and anti- 
toxic. 

14. Since the efficiency of curative serums is increased many 
fold when administered intravenously, this route will be used more 
frequently than has been the custom in the past. 



A CONSIDERATION OF AUTOGENOUS VACCINES. 

By B. B. Vincent Lyon, A.B., M.D. 
Pathologist to Methodist Episcopal Hospital; Assistant Pathologist to German 

Hospital, Philadelphia. 

Empiricism is dying. Throughout the last century, and par- 
ticularly its latter decades, the searchlight of truth has lighted up 
many of the heretofore dark places in the study and practice of 
medicine. The discovery of the causation of many diseases through 
bacterial agencies was epoch-making, and led the way naturally 
toward the introduction of measures able to cope with such a foe. 

During the last thirty years scores of men have been at work on 
this problem and have each added their little to the sum of our 
present knowledge, and from the time of Jenner one startling 
etiologic and therapeutic discovery has followed another, so that 
among the names destined to live will always be found those of 



Am. Jour. Pharm. 

May, 1914. 



Autogenous Vaccines. 



207 



Pasteur, Koch, Pfeiffer, Ehrlich, Behring, Wassermann, Noguchi, 
and others. 

Bacteria are divided into two classes, the good and the bad: 
saprophytic and pathogenic. The saprophytic bacteria are scav- 
engers; they thrive best on dead tissues and assist in freeing the 
body of many waste products. Pathogenic bacteria thrive best on 
the living tissues of the host, in whom they are capable of producing 
disease. Their pathogenic action is due to the liberation of the 
toxins they contain or the elaboration of poisons in the tissues 
of the host. 

Of these bacterial toxins there are two main types: The exo- 
toxins, contained in bacteria whose poisonous principles are capable 
of being dissolved out of the bacterial cell. To this class belong the 
bacillus of diphtheria and the bacillus of tetanus. The great ma- 
jority of bacteria, however, produce endotoxins, or poisons which 
are incapable of separation from the cell bodies by any of our 
known filtration methods. Examples of this are the bacillus of 
typhoid fever and the streptococcic and staphylococcic groups, etc. 

While bacteria are capable of producing disease, it is not through 
their mere presence per se, for, as we know, our persons in health 
permit of the culturization of numerous pathogenic bacteria, there- 
fore other factors must enter in, and these factors comprise the 
natural defensive mechanism of the body against disease. 

Natural Resistance. — This varies greatly with the individual 
and has a certain selective action, for why is it that one person 
can harbor in his mouth virulent pneumococci and streptococci and 
yet can go through life without a single attack of pneumonia, and, 
conversely, be subject to repeated attacks of tonsillitis ; whereas, 
another individual harboring the same organisms may have several 
attacks of pneumonia during his lifetime, and none of tonsillitis. 
This is due to the development of what we call immunity, which is 
the power of resistance the body tissues are able to exert against 
bacterial poisons. Immunity may be divided into species and racial 
immunity. 

Species Immunity. — It is well known that many animals are 
naturally immune to diseases common to man, and that it is only 
with the greatest experimental difficulties that infections with those 
diseases can be made successfully. 

Racial Immunity. — Also, among the different races of the same 
species there appears to be a natural immunity against certain 



208 



Autogenous Vaccines. 



Am. Jour. Pharm. 
May, 1914. 



diseases, which have long been prevalent in that particular section, 
but which when carried to another section where fresh soil is 
obtained immediately light up into virulent epidemics. This is seen 
in the ravages of tuberculosis among the negroes and American 
Indians, and it is seen conversely in the immunity from yellow 
fever that has long been enjoyed by the negro. 

Acquired immunity is the protection that is afforded an in- 
dividual who has passed through an attack of one disease, this con- 
ferring a greater resistance to that disease in the future. This is 
commonly observed in diseases like typhoid and yellow fever. Ac- 
quired immunity may be either active or passive. " The process 
of conferring protection by treatment with either an attenuated 
form or a sublethal quantity of the infectious agent of a disease or 
its products is spoken of as active immunization," because the 
immunized individuals gain their power of resistance by taking 
an active physiological part in the acquisition of this new property 
of immunity. Thus active immunity can be acquired by repeated 
injections of attenuated cultures, as in Pasteur's work in hog 
cholera; by injections of sublethal doses of virulent bacteria, as 
demonstrated in the protozoon disease of Texas fever; by injections 
of killed bacteria, first suggested by Chauveau. This method of 
active immunization with gradually increasing doses of killed bac- 
teria has been carried out successfully against many bacterial 
diseases. It is particularly useful against those groups of bacteria 
producing endotoxin; and, finally, by injections with bacterial 
products from poisons excreted or liberated from the bacterial cell 
body. These measures comprise vaccination. 

Passive immunity, on the contrary, is that gained by the host 
through no active formation of antibodies on its own part, but 
rather accepting ready to hand the antibodies prepared by the 
tissues of another species. The most conspicuous types of this are 
the antidiphtheritic and antitetanic sera. These are both designed 
to meet bacterial exotoxins, and it is this type of sera that is most 
successful. On the contrary, antigonococcic, antistreptococcic sera, 
and the like, which depend for their activity on the lysin, opsonin, 
and other antibodies they contain, are not blessed with a like thera- 
peutic success. Allen states that " these sera are not always cura- 
tive ; indeed, their use during active disease may not be altogether 
free from danger. Thus the administration of anticholera or anti- 
typhoid serum, which each depend for their activity on the lysin 



Am. Jour. Phann. 
May, 1914. 



Autogenous Vaccines. 



209 



they contain, may result in the extraleucocytic lysis of so many 
bacteria that the resultant flooding of the tissues with large quan- 
tities of their contained endotoxin may imperil the life of the 
recipient from the additional toxaemia." 

Bacteria have a selective action : not only must they gain access 
to the body in large enough numbers and possessing sufficient 
virulence, but they must also gain entrance to a tissue that is suit- 
able for their further development. For instance, you can rub a 
typhoid culture into an abraded surface of the arm or a culture 
of streptococci can be swallowed, both with equal impunity, but 
reversing the conditions a bacterial infection is sure to follow. 

Now what are the general defences of the body against this 
bacterial invasion ? They are fourfold : 

1. Antitoxin, a substance manufactured by the tissues which 
is capable of neutralizing the soluble toxins produced by certain 
groups of bacteria. 

2. Agglutinin, a substance which causes bacteria free in the 
tissues or blood stream to be clumped together in masses and held 
nearly immovable and therefore more accessible for phagocytosis. 
This is the more conspicuous where it concerns the motile bacteria. 
Though originally observed in 1889 by Charrin and Rogers, in 
studying the Bacillus pyocyaneus, the agglutination reaction is com- 
monly associated with Widal, who first applied the phenomenon in 
the diagnosis of disease by an unknown organism. 

3. Lysin, a substance or substances elaborated by the body which 
has the property of dissolving certain bacteria. PfeifTer noted that 
guinea pigs which had been immunized against cholera bacilli could 
withstand the further intra-peritoneal injection of virulent cultures 
without harm, and found that the peritoneal fluids dissolved the 
organisms. 

4. Opsonin, discovered and named by Wright, is a substance that 
prepares or sensitizes the bacteria for ingestion by the phagocytic 
elements of the white blood-corpuscles. 

There are two types of bacterial infection : local and general. 
The former is best represented by boils ; the latter is seen in diseases 
like typhoid fever, pneumonia, puerperal sepsis, and the like. When 
a person recovers from a bacterial disease like typhoid fever, it is 
by the body having gradually elaborated the foregoing antitoxins, 
agglutinins, lysins, and opsonins in amounts sufficient to cause the 
neutralization, destruction, and solution of the bacteria. The time 



210 



Autogenous Vaccines. 



(Am. Jour. Pharm. 
\ May, 1914. 



required in the manufacture of these substances varies in different 
diseases: 21 to 28 days, as a rule, in typhoid fever; 9 to 11 days, 
as a rule, in pneumonia, etc. So we have two biologic methods of 
treatment, serum and vaccine treatment, and the principle of the 
former is to supply these protective substances ready made (passive 
immunity) and in vaccination to stimulate the tissues to produce 
them more quickly, and, inasmuch as diseased tissues are more 
sluggish in locally manufacturing them, to utilize or exploit healthy 
tissues for the advantage of the enfeebled ones (active immunity). 
This, then, is the scientific basis for the action of vaccines. And now 
what are vaccines? 

Vaccines are emulsions of the bodies of dead bacteria killed in 
various ways and suspended in suitable dosage in solution of nor- 
mal saline. 

There are two types of vaccines : heterogenous and autogenous. 
Heterogenous vaccines are prepared from infections similar to the 
case which is to be treated, but from infected material not derived 
from the patient himself. This type of vaccine may be, and usually 
is, polyvalent; that is, cultures are obtained from several infections 
of the same nature and therefore represent, possibly, several 
" strains " of the same organism. These heterogenous vaccines are 
commonly called " stock " vaccines, perhaps because they are pre- 
pared in quantities and held in readiness to be used in a given case 
on demand. i • ' H L j i 

: !-''■ ' ! ; Li!; m I 1 

Autogenous vaccines are prepared from cultures grown from in- 
fected material obtained from the patient himself. In other words, 
they represent and are specifically the organism from the effects of 
which the patient is suffering and toward which you are assisting 
the patient to establish an immunity. Knowing these differences, 
it is not difficult to understand that biologists, bacteriologists, se- 
rologists, and clinicians of the thinking type are agreed that the 
autogenous group of vaccines fulfil best the scientific therapeutic 
requirements. Let me quote from an article recently published 
by a man whose authority is unquestioned : " With the exception 
of certain organisms, such as tubercle bacillus and the gonococcus, 
there is little reason for employing stock vaccines instead of au- 
togenous, and there is abundant ground for believing that the use 
of stock vaccines will not only lead to carelessness of diagnosis and 
misinterpretation of the probable nature of the infection with con- 
sequent administration of the wrong species, but will sometimes 
be directly harmful. 



Am. Jour. Pharm. 
May, 1914. 



Autogenous Vaccines. 



211 



" I am well aware that the argument has been advanced that 
laboratories are not sufficiently- available to practitioners in all sec- 
tions to make it possible for them to obtain autogenous vaccines, 
and would reply that in a measure this may sometimes be true; but 
the general demand for stock vaccines has been artificially stimulated 
by manufacturers, and the practical application of this method of 
treatment has outdistanced the scientific investigation of its merits. 
Instead of wholesome growth with the gradual provisions of local 
agencies where autogenous vaccines could be obtained, an unwhole- 
some growth of this mode of treatment has been stimulated, 
and those who seek to keep up with the latest pronouncement of 
advertisement literature find themselves in a position of dependence 
upon stock vaccines in many cases. There can be no doubt that in 
some instances stock vaccines are satisfactory. Staphylococcus 
and typhoid , and tuberculosis vaccine are instances, but the other 
forms, and especially streptococcus and pneumococcus and mixed 
vaccines, are of very doubtful efficacy. 

" Here we come upon the field of variability in the organisms 
themselves, and, unless a growth has been prepared from the 
patient himself, the strain may be entirely different and inappro- 
priate. It avails little to use mixed strains which require the reduc- 
tion of dosage of the one possibly present and available strain 
below the point of usefulness because of the simultaneous injection 
of several other strains in the mixture which are of no use, or 
practically useless. 

" As for stock mixture of heterogenous organisms designed 
for the treatment of cases in which no sort of accurate bacterio- 
logical diagnosis has been made, too vigorous condemnation cannot 
be phrased." 

In my own personal experience I have met with many cases 
referred to me by other practitioners, cases on whom various 
■ stock vaccines had been tried for various lengths of time, in various 
dosages, with absolutely no improvement, and which have responded 
with surprising promptness to an autogenous vaccine, and have 
established an immunity that in many cases has lasted for years, 
and I personally have used in some cases stock vaccines of different 
types, giving them a thorough trial, only to become discouraged at 
their non-success, and have discarded them in given cases for 
autogenous vaccines with gratifying results. 

On the other hand, I believe that stock vaccines of a single 



212 



Autogenous Vaccines. 



Am. Jour. Pharm. 
May, 1914. 



or of a polyvalent single organism type have their place, and a very 
important place of usefulness, in the 48-96 hour interval that is 
often necessary to prepare the autogenous vaccine, after the bac- 
terial identification in the specific case has been established, and I 
almost uniformly use this period to give one and sometimes two 
injections of the appropriate stock culture. Appropriate stock 
cultures may often be used with value in association with autogenous 
vaccines in selected cases. 

A word or two now to ensure success in getting the proper 
bacterial results in culture taking. The first principle is to obtain 
your material free from contamination, and this requires the observ- 
ance of special precautions according to the kind of material that 
is to be cultured. 

Urine: Should always be obtained by sterile catheter, after the 
external meatus has been appropriately cleansed, and drawn off into 
a sterilized flask or bottle, to which no preservative should be added. 
It is better to catheterize the day specimen into one receptacle and 
the night urine into a separate one. 

Feces: Should be obtained, urine- free, and specimens from first 
and last portion of the stool obtained and studied. 

Sputum: Should be obtained with greatest care, because for 
practical purposes no mouth is germ-free, and alveolar pyorrhoea, 
infected tonsils, and the like are so common. Before retiring, the 
mouth should be carefully rinsed with sterile water and the teeth 
brushed with sterile toothbrush, and a closed vessel containing 
sterile water placed at the bedside. In the morning the mouth 
should again be rinsed thoroughly with the sterile water, gargled, 
and with the brush re-sterilized, by dipping in boiling water, the 
teeth should be thoroughly brushed and then a few mouthfuls of 
clean sterile water should be swallowed. After this the sputum 
should be expelled by coughing and caught in serial sterilized wide- 
mouth bottles (with sterile corks), and it is best that only one or 
two masses of sputum should be expelled into any one bottle and 
the bottles labelled and sent at once to the bacteriologist for im- 
mediate examination. The sputum should, after direct examination 
of stained specimens to determine morphologically the different 
types that may be present, be then " whipped " through several 
Petri dishes containing sterile water to further free the bacteria 
from surface contamination, and the final washed specimen planted 
upon the different culture media that will appear best suited for 



Am. Jour. Pharm. 
May, 1914. 



Autogenous Vaccines. 



213 



their recovery in pilre culture, as judged from the findings on the 
first direct examination. 

Cultures taken from boils, or from infected sinuses, from acne 
pustules, from tonsillar follicles, and the like, should be made only 
after thorough appropriate cleansing and disinfection of surface 
relations, and then taken from a second or third portion of the 
material, discarding the first, by means of a platinum wire or a 
sterile capillary glass pipette inserted well within the cavity. 

Cultures from eye, ear, or nose should have appropriate measures 
to secure success. 

Blood specimens should always be obtained from a vein, pref- 
erably at the bend of the elbow, by means of an all-glass sterilized 
syringe of a capacity not less 'than 5 c.c. It is rarely necessary 
to cut down on a vein, but the arm should be thoroughly sterilized 
by tincture of green soap and water, by 5-10 per cent, lysol, by 
absolute alcohol, and finally by ether; personally I prefer not to use 
iodine. It is better to moderately tourniquet the upper arm before 
sterilizing the field in order to prevent thin- walled veins from col- 
lapsing under the pressure. The blood should be immediately plated 
and flasked in peptone and dextrosed broth. 

In Pulmonary Abscesses: In suitable cases material may be 
obtained by lung puncture in the following way : After sterilizing 
the chest wall in the same manner as for blood cultures, the needle 
attached to an all-glass syringe, containing 3 c.c. of peptone broth, 
should be plunged into the lung at the proper point, as determined 
beforehand by clinical means, and 1 c.c. of the broth introduced 
and then reaspirated as far as possible and tubed. This measure 
will yield results in many cases properly selected clinically. 

After getting suspected* infected material, direct examination by 
means of variously-stained slide specimens should be made to 
determine morphologically and by staining reactions and relations 
whether one or more types of organisms are present, and, if the 
latter, how many and what types, and then, aided by this knowledge, 
proceed to utilize the various culture media that will best ensure 
recovery of each organism in pure culture. Here is where the 
thoroughly-trained bacteriologist will succeed and in the shortest 
time. It is often exceedingly difficult to recover a shyly-growing 
streptococcus or tubercle bacillus occurring in small numbers, let us 
say from a urine practically alive with the Bacillus coli. This may 
be accomplished by inhibiting or attenuating the growth of the 



214 



Autogenous Vaccines. 



{Am. Jour. Pharm. 
May, 1914. 



hardier, more freely growing organism by treating the culture 
medium in an appropriate manner, but unless this is accomplished 
it will be seen at once how useless it is to successfully treat a 
pyelitis of streptococcal or tubercular origin by using only the 
B. coli in the vaccine preparation. Hence the failure of many 
autogenous vaccines that are bacteriologically imperfect or in- 
complete. 

In many cases of chronic gleet, however, the gonococcus is 
absent and the catarrhal inflammation kept alive by secondary in- 
vaders, which may then in combination serve for cure in absence of 
the primary invader. 

After getting out every bacterial group contained in a given 
specimen, each in pure culture, these should then be studied with a 
view to their share in the production or continuation of the disease 
in question, and, guided by experience, clinical as well as bacterio- 
logical, a final judgment of the organisms concerned may be passed 
and the proper ones selected for use in the vaccine. They may 
all be combined in a single ampoule or may be placed singly or in 
pairs. Only the lower dosages, however, can be reached by making 
a mixed vaccine composed of many elements, on account of the 
combined dosage being too high to permit of safe injection. 

We can now proceed to prepare the vaccine, in which the 
following steps are concerned: 

1. To obtain an emulsion containing the bacteria in purity — an 
emulsion with a uniform suspension and as free from bacterial 
clumping as possible. 

2. To standardize the emulsion — that is, to determine how 
many bacteria are contained in each cubic centimetre. 

3. To kill the bacteria in the emulsion and then tube them — or 

4. To decide upon the dosage of each ampoule or set of am- 
poules ; to tube them still alive and then kill them. 

5. To label, effectively, each ampoule and place them in sets 
of ten in compartment boxes or cartons, the lids of which are to be 
specifically marked with the names of the organisms they contain 
and in what dosage, and most particularly with directions for their 
use. 

6. To be sure that all " controls " are sterile before allowing 
the vaccine set to leave the laboratory for use. 

I shall not in this paper enter in detail into the technic required 
in the actual preparation of the vaccine, but I want to say a word 



Am. Jour. Pharm. 
May, 1914. 



Autogenous Vaccines. 



215 



or two of caution to most carefully consider the best ways of killing 
the bacteria without impairing .their immunizing properties. This 
can only be accomplished by a thorough knowledge of and observ- 
ance of the thermal and chemical death-point of each group of organ- 
isms : a knowledge that will tell you which bacteria should be 
killed by heat and which by chemical measures, or by a combination 
of the two. If by heat, at what temperature and for how long 
sustained ? If by chemical sterilization, by what chemical and in what 
strength? I have known many an autogenous vaccine — otherwise 
quite appropriately selected bacteriologically and otherwise fault- 
lessly prepared — to be inert and to fail absolutely therapeutically 
for no other reason than that the thermal and chemical death-points 
were not carefully ascertained. And I doubt not that this applies 
equally to many stock vaccines. 

Have we in vaccine therapy a means sufficient to combat all 
types of bacterial infections? I would answer emphatically "no," 
and I would add that harm may often come from their indiscriminate 
use and in the hands of the inexperienced and careless. 

In epidemic meningitis, in typhoid fever, in pneumonia, in gen- 
eralized bacteremia, with or without ulcerative endocardial lesions, 
the use of vaccines for curative purposes has not been attended 
with great success, although occasionally a case is seen in which 
amelioration in severity of symptoms has taken place which rightly 
or wrongly has been ascribed to the use of the vaccine. I am by no 
means yet convinced that their use in such cases is unjustifiable, 
and believe that we may yet arrive by experience at some method 
of establishing proper dosages and proper intervals of injection 
for this class of acute fulminating infections that will produce 
better results. 

The most suitable field for vaccines and the field in which the 
most brilliant results have been obtained lies in treatment of 
diseases, acute or chronic, that have a local focus of infection, such 
as furunculosis, carbuncles, abscesses, various bone infections, such 
as osteomyelitis, various skin infections, such as acne vulgaris, 
infected sinuses, pyelitis, empyema, various infections of the mouth, 
such as pyorrhoea alveolaris, infections of the nose and nasal pas- 
sages and various post-gonorrhceal conditions, and various con- 
ditions of the respiratory tract. 

And now a final word as to why vaccines fail in the hands of 
many workers, even in the above field of election — chiefly because 



216 Chemistry of a Cup of Coffee. | A %^ 9 P i4 arm ' 

of insufficient knowledge governing the general laws of dosage and 
time intervals of injection; by selecting inappropriate points of 
injection; by disregarding the best time of day at which injection 
should be given, so that the patient isn't safeguarded during the 
" negative phase " period at which his antibody formation is at the 
lowest ebb, etc. For many of these points I would refer the student 
or interested worker to a close perusal of monographs on this sub- 
ject, notably Allen on " Vaccine Therapy." 

Finally, I would call attention to a common cause of failure in 
a neglect to realize that autogenous vaccines need to be frequently 
freshly renewed — i.e., a new culture taken and a new vaccine pre- 
pared from cultures that represent more nearly the status prcusens 
of the case; for it frequently happens that in long chronic con- 
ditions the bacteria, by mutation or other biological properties, be- 
come adapted more or less to the antibodies formed in the tissues 
of the host. 

I was asked, before reading this paper before this body, whether 
I did not think it quite feasible and quite proper for druggists to 
establish autogenous and stock vaccine departments for the purpose 
of themselves making these products. I think I must already have 
answered this question to most of you. I do not think it is practical 
nor fitting that you should, nor do I believe that it would prove 
commercially a success. And let me close with the words of Sir 
Almroth Wright, one of the pioneers in this work, who states that 
for such skilled service as that demanded for vaccine therapy " is 
required a man who has spent years of study to master the technic ; 
to know how to make the vaccines, to know where to look for 
the microbes, to know how to isolate them, and, most of all, a man 
with sufficient experience and ability to apply all these things." 

1901 Pine Street, Philadelphia, Pa. 



THE CHEMISTRY OF A CUP OF COFFEE. 

From time to time numerous analyses of coffee have been made 
and published which, while giving some insight into- the chemistry 
of the coffee berry, have not necessarily enlightened us as to the 
position of affairs in regard to the liquor obtained when coffee is 
prepared in the way commonly enjoined. The chemistry of the cup 
of coffee will obviously leave out of consideration the chemistry of 



Am. Jour. Pharna. 1 
May, 1914. / 



Chemistry of a Cup of Coffee. 



217 



the " grounds." It is the infusion with which the following labora- 
tory notes deal, and certain fresh indications, we believe, have been 
obtained which are worth presenting in view of their medical in- 
terest. The story is far from complete, but there are interesting 
incidents in it which, as far as it goes, are worth recording. 



A Comparison between Coffee and Tea. 

From a pharmacological or, what should amount to the same, a 
dietetic standpoint tea or coffee ought in certain ways, at all events, 
to act similarly, since both contain the alkaloid caffeine which has a 
well-known and marked effect of stimulation upon the central 
nervous system. It is generally admitted, however, that the two 
beverages, though having one thing in common, afford different 
results. Tea, it is well to point out, contains a much larger propor- 
tion of the alkaloid than coffee, but in the preparation of tea in 
ordinary domestic practice a much smaller quantity of material is 
used than is the case with coffee. A common formula enjoined in 
the making of tea amounts to the preparation of 1.25 per cent, in- 
fusion of the leaf. Similarly, in the preparation of coffee the quan- 
tity of coffee usually directed to be used signifies a 6 per cent, decoc- 
tion. Since tea contains from 3 to 4 per cent, of caffeine, and 
coffee seldom more than 1 per cent., it follows that as regards this 
alkaloid both infusions of coffee and tea made on common domestic 
lines will contain practically the same amount of caffeine volume for 
volume of fluid. The inference is that whether it be a cup of coffee 
or of tea, the dose of alkaloid will be the same. But according to 
the present investigation the caffeine in coffee infusion has quite 
different associates from those in tea. This would appear to be the 
case, inasmuch as while little caffeine is extracted from tea by cold 
water, we find that practically the whole of the caffeine in coffee is 
taken out. There seems to be little doubt, as we have shown in pre- 
vious articles upon tea, 1 that the caffeine in tea is for the most part 
combined with tannin in the form of caffeine tannate, which is not 
very soluble in cold water, but is easily soluble in hot water. We 
think this is an important observation, for it points to the proba- 
bility of caffeine existing in coffee in a quite different form which is 

1 " The Chemistry, Physiology, and ^Esthetics of a Cup of Tea," The 
Lancet, Jan. 7th, 191 1, and Dec. 2nd, 191 1. 



218 Chemistry of a Cup of Coffee. { A % J a Xi 9 P il arm ' 

easily soluble in cold water. Subsequent experiments showed that 
the caffeine in coffee is combined with a peculiar acid allied possibly 
to tannic acid, but exhibiting different properties from the tannin 
present in tea. Thus this acid (it has been called caffetannic acid by 
some observers) is not particularly astringent, has a sour coffee-like 
taste, does not coagulate gelatin, gives a light green colouration with 
perchloride of iron (whereas tannic acid of tea turns it black), does 
not make caffeine solutions thick as does tannic acid, does not pre- 
cipitate alkaloids — e.g., quinine — and, in fact, shows altogether dif- 
ferent properties from the tannic acid of tea. It gives a precipitate, 
however, with lead acetate from which the acid can be separated by 
sulphuretted hydrogen. When coffee infusion is saturated with 
ammonium sulphate a precipitate is obtained which contains a small 
proportion of the total caffeine in the free state, whereas a tea infu- 
sion similarly treated gives an abundant precipitate containing nearly 
all of the caffeine, this precipitate according to our observations con- 
sisting chiefly of caffeine tannate. 

The Absorption of Caffeine Modified by its Associates. 

The caffeine tannate of tea is precipitated by weak acids, and the * 
presumption is that it is precipitated by the gastric juice, and there- 
fore the caffeine is probably not absorbed until it reaches the alkaline 
alimentary tract. In the case of coffee, however, in whatever form 
the caffeine may be present, it is soluble in both alkaline and acid 
fluids, and therefore the absorption of the alkaloid probably takes 
place in the stomach. This fact may have an important physiological 
significance when we consider the comparative stimulating effects of 
the two beverages. If our view is correct coffee should act more 
promptly than tea as a stimulant and restorative, looking to its 
physiological action as due for the most part to caffeine. In prac- 
tice it is generally accepted that coffee is a more powerful restorative 
than tea. The use of strong coffee as an antidote in poisoning by 
narcotics, notably morphia, is of interest in this connexion. Tea is 
mentioned for the same purpose, but only rarely. Apart from 
the consideration that caffeine has probably a more rapid action 
when taken in the form of coffee than in the form of tea, because 
the caffeine in coffee is more readily absorbed, it must also be re- 
membered that coffee is often made with a generous proportion of 
the powdered bean, as in the case of the after-dinner " black " coffee, 



' m 'M J a°y Ur i9i4 arm "} Chemistry of a Cup of Coffee. 219 

the view being that the secret of good coffee is to make it strong. 
This, of course, is an entirely aesthetic demand, which may likely 
enough be opposed to physiological morality. 



The Strength of Cold Water Extracts of Coffee Compared 
with Boiling Water Extracts. 

The fact that the caffeine in coffee is completely soluble in cold 
water suggested making a comparison as to the composition of the 
cold and hot water infusions in regard to other constituents. For 
this purpose several types of coffee were chosen, all of which reached 
this country through Costa Rica. As will be seen from the accom- 
panying table, the varieties examined were as follows : Raw {i.e., 
unroasted) Costa Rica, common quality; raw Costa Rica, finest 
quality ; pale roasted Costa Rica, common quality ; pale roasted Costa 
Rica, finest quality ; high roasted Costa Rica, common quality ; and 
high roasted Costa Rica, finest quality. The results are instructive, 
and we may proceed to consider the differences in composition of 
the infusions, both cold and hot, shown where raw, pale roasted, 
and high roasted coffee are employed, and the relationships, if any, 
of these differences to the discrimination supplied by the expert 
taster, who describes a particular coffee as, in his own words, " com- 
mon " or " finest." 

It is a somewhat remarkable fact that cold water extracts from 
coffee the same weight of materials as boiling water, but it must 
be admitted that the former infusion is somewhat less palatable 
than the latter. Chemically, however, there is little difference be- 
tween them, and we may presume that physiologically a cold water 
extract of coffee will be much the same as a hot water infusion, leav- 
ing out aesthetic considerations, although these, of course, are exceed- 
ingly important, from all dietetic aspects. It is probable that cold 
water fails to extract certain oily bodies or fats which contribute 
attractive taste and aroma. The total extract is frequently higher 
in cold than in hot water. And not only is caffeine extracted from 
coffee equally well by cold and hot water, but this is true of the 
mineral salts and of the peculiar acid known as caffetannic acid, the 
acid which corresponds to the tannin of tea. In regard to the pro- 
portion of materials soluble in cold water coffee shows an entirely 
different result to tea, inasmuch as while coffee yields about 25 per 
cent, of its weight to cold water (an amount which is not increased 



220 



Chemistry of a Cup of Coffee. { 



Am. Jour. Pharm. 
May, 1914. 



when hot water is used) tea yields only 12 per cent, of its weight to 
cold water, which is increased to 25 per cent, when the infusion is 
made with hot water. Again, cold water extracts from tea only 17.5 
per cent, of its total caffeine, while from coffee it extracts the whole. 
Similarly, cold water extracts from tea 13 per cent, of its total tan- 
nin, while coffee under the same treatment yields practically the 
whole of its caffetannic acid. 

The Effect of Roasting. 

An infusion of green or unroasted coffee is singularly nasty to 
the palate, and it follows that the roasting process renders coffee 
the palatable article that it is. The chemistry of roasting amounts 
largely to a caramelisation process, during which certain oils and 
aromatic principles are formed as products of a mild destructive dis- 
tillation. Curiously enough, there is little loss of caffeine in this 
process, as our results show, which is remarkable in view of the 
fact that caffeine sublimes at high temperatures. There are two 
degrees of roasting adopted — viz., pale roasting and high roasting. 
The important chemical effect of roasting, according to our analyses, 
is to diminish considerably the amount of caffetannic acid. If the 
figures in the table be consulted it will be seen that while in an 



The Analysis of Hot and Cold Infusions of Coffee. 



Constituent. 


Raw Costa Rica 
(common). 


Raw Costa Rica 
(finest). 


Pale roasted Costa 
Rica (common). 


Hot 
infusion. 


Cold 
infusion. 


Hot 
infusion. 


Cold 
infusion. 


Hot 
infusion. 


Cold 
infusion. 


Total extract 

Ash of extract 

Caffetannic acid 


29.16 
4.16 
9.60 
1. 00 


30.83 
3-88 
8.63 
1-33 


29.60 
4.00 
9.66 
1. 21 


3i.5o 
3-88 
7.83 
1.56 


25-33 
4.16 
6.10 
1. 11 


24.00 
5-66 
5.8o 
1. 11 


Constituent. 


Pale roasted Costa 
Rica (finest). 


High roasted Costa 
Rica (common). 


High roasted Costa 
Rica (finest). 


Hot 
infusion 


Cold 
infusion. 


Hot 
infusion. 


m Cold 
infusion. 


Hot 
infusion 


Cold 
infusion. 




23.SO 


25.66 


24.30 


24.00 


25.60 


23.00 




3-50 


4-50 


4.66 


4.00 


4.00 


4-50 


Caffetannic acid 


6.60 


5-90 


3-90 


3.16 


363 


3.87 


Total caffeine 


1. os 


1.06 


1.23 


1. 11 


1.05 


1.20 



Am. Jour. Pharm. 
May, 1914. 



Chemistry of a Cup of Coffee. 



221 



infusion of raw coffee (unroasted) the caffetannic acid amounts to 
9.60 per cent., it is in the pale roasted 6.60 per cent., while by 
further roasting, as in the " high roasted," it is reduced in the 
infusion from 3.63 to 3.90 per cent. What part cafTetannic acid ex- 
actly plays as a dietetic constituent of coffee it is difficult to say, 
but if it should prove to be an undesirable element, then the high 
roasted coffees are least open to objection on this account. It may 
be noticed also that the raw coffee yields a greater percentage of 
soluble constituents to both cold and hot water than high roasted 
coffee, the pale roasted coffee showing intermediate results. Roast- 
ing, amongst other things, has, therefore, the effect probably of 
rendering certain bodies insoluble — e.g., albumins — while the slight 
burning effect upon carbohydrates would produce possibly some free 
and of course insoluble carbon. 

Quality of Coffee in Relation to Chemical Composition. 

From the results recorded in the table it will be seen that no 
definite relation cambe traced between the aesthetic quality of coffees, 
classed respectively as " common " and " finest," and the chemical 
composition of the infusions which they yield. It may be noted that 
there is no important difference in the amount of the drug caffeine 
when the common and finest varieties are examined. It is probable 
that the aesthetic values — flavour, body, aroma, and so forth — are re- 
lated in some way to the amounts of oil bases or aromatic principles 
present, and these are in any case minute. Whether they are present 
in appreciable quantity or not doubtless depends upon the care spent 
upon the roasting process. At any rate, it is conceivable that a point 
in the roasting process could be reached which would deprive the 
coffee of all attractive flavour, while it is certain that the infusion of 
the raw unroasted berry is not fit to drink on account of its un- 
pleasant taste. Recently it has been announced on more than one 
occasion that pyridin is an important constituent of coffee. We have 
certainly found it present, but not in sufficient quantities to estimate. 
It is rather a curious fact that some authorities mention that coffee 
often relieves asthma, while pyridin is described as " useful in the 
treatment of asthma " and " beneficial in cardiac dyspnoea, emphy- 
sema, and angina pectoris," and, finally, that " it is probably the 
relieving agent of various cigarettes and powders smoked or burnt 
for asthma and whooping-cough." Another constituent of coffee 



222 



Chemistry of a Cup of Coffee. 



Am. Jour. Pharm. 
May, 1914. 



produced by roasting is caffeol, a nitrogen-containing oil, but it 
would be impossible to differentiate the quality of coffee upon an 
analysis pursued in this direction, inasmuch as the amount found 
does not exceed more than 0.06 per cent. It is doubtful whether it 
has any further value from a dietetic point of view than that sup- 
plied by its influence in pleasing the senses. When isolating caffeine 
from coffee infusion the solvent (chloroform) takes out also a non- 
crystalline substance which unlike caffeine is soluble in ether. This 
substance has a very strong, pleasant, but somewhat bitter flavour 
of coffee. The yield is different according to the quality of the 
coffee examined, and it is possible that this principle is a determining 
factor in the judgment given by the expert coffee taster. It is a 
product of roasting and does not exist in raw coffee. 

Food Value of Coffee. 

The infusion of coffee presents practically very little material 
that is of direct nourishing value, but by diminishing nervous 
fatigue, by virtue chiefly of the caffeine present, it may increase 
muscular power. It is not itself a builder of tissue. The use of coffee 
after dinner, it is of interest to note, is justified in a large number 
of cases by the fact of its stimulating effect upon the vital centres, 
and it is said to serve to some extent as an antidote to alcohol. It 
is commonly claimed to remove drowsiness ; as a matter of fact, 
in many subjects it produces drowsiness, but this is usually followed 
quickly by marked wakefulness. The practice of drinking coffee 
after a meal for the sake of the stimulus which is experienced has 
much to be said in its favour dietetically. There is no reason for sup- 
posing that coffee possesses any value as a food. The berry con- 
tains a quite important proportion of fatty substances (12 per cent, 
average), but these are necessarily excluded from the infusion, as 
owing to their insolubility they remain in the " grounds." 

According to our analyses again the protein contents of a cup 
of coffee are small, approximating to 1.25 per cent, of the coffee 
extracted. This amount can have little dietetic significance. There 
is also a trifling quantity of dextrin and sugar present besides traces 
of alcohol, which again can possess no importance from a physio- 
logical point of view. — The Lancet, Nov. 29, 1913, pp. 1 563-1 565. 



Am. Jour. Pharm. 
May, 1914. 



Book Reviews. 



223 



BOOK REVIEWS. 

Pharmaceutical Botany. By Heber W. Youngken, Assistant 
Professor of Botany and Pharmacognosy at the Medico-Chirnrgical 
College, Philadelphia. P. Blakiston's Son & Co., Philadelphia. 

To speak of this little book of less than a hundred pages as a 
dictionary or a glossary is not to belittle its value to the student. The 
illustrations, as, for example, those on stem and leaf structure, are 
especially well chosen, and their pictorial value is worth many words 
of text, which, of course, is not a factor of this book. From almost 
any aspect of thought the book seems like a list of terms, but these 
terms are well arranged and with a good regard to system. The 
desire to make the definitions brief has made them in many cases 
almost meaningless except just as a reminder to one who already 
knows what the term means. 

As a whole, the acknowledged desire of the author has been well 
attained, but there is a question whether such an object is especially 
advisable. A student is apt to* be just as human as the average per- 
son with a consequent eagerness to have before him a volume which 
is " readable " even though it is for purposes of study. The feeling 
arises in us, as we look over the volume in hand, that it is a mighty 
nice little book to turn to once in a while, but that it would rather 
strain our devotion to science if we were called upon to use it as a 
text-book from which to gain our first insight into a new subject. 

A. K. Lobeck. 

Annual Reprint of the Reports of the Council on Phar- 
macy and Chemistry of the American Medical Association 
for 1913, with the Comments that have appeared in the Journal. 

" The more strictly scientific parts of the reports, both from lack 
of space and because of their technical nature, have been abstracted 
or entirely omitted from the reports as published in the Journal. 
Believing that these scientific investigations should be available to 
scientists in general, especially to chemists, pharmacologists, and 
others interested in medicine, the Council has authorized the prep- 
aration of this volume, containing the complete reports of the Coun- 
cil adopted prior to January 1, 19 14, as well as the comments which 
have appeared at the time of publication." 

These reports are a valuable addition to the literature that has 



224 



Current Literature. 



Am. Jour. Pharm. 
May, 1914. 



accumulated in the last few years on proprietary remedies and 
nostrums. 

Previous to the last decade investigative work of this sort in 
reference to remedies of this kind was hardly thought of, although 
there may have been dreamers who had hopes and visions of what 
the future might bring forth. We do not use the word " dreamers " 
in any offensive sense. Dreamers with initiative and honesty of 
purpose are the compelling force in this world, and it is gratifying 
to know that there are men of this type in medicine and pharmacy 
who are willing to work disinterestedly for the body politic. 

Pharmacists who desire to add to their efficiency and usefulness 
would do well to add these reports, which have been appearing for 
several years, to their libary. 

John K. Thum. 

New and Nonofficial Remedies, 1914: Containing Descrip- 
tions of the articles which have been Accepted by the Council on 
Pharmacy and Chemistry of the American Medical Association 
Prior to January 1, 1914. 

This work epitomizes one phase of the revolution that has taken 
place in medicine the last decade. It typifies the passing from dark- 
ness into the light of reason of things pharmacological, or rather the 
exploitation of modern materia medica. Indeed, it fills a long-felt 
want in both the profession of medicine and pharmacy. When one 
stops to consider the inaccessibility of information relating to un- 
official remedies previous to its publication it hardly seems possible 
that we ever got along without it. 

Essential information relating to biological remedies such as 
serums, vaccines, and tuberculin preparations is given in a manner 
convenient to the seeker after such knowledge. 

John K. Thum. 



CURRENT LITERATURE. 

Uniformity in Drug Standards. — In a contribution to the 
Journal of the Kansas State Medical Society, entitled "A Plea for 
Uniformity in Drug Standards and for Uniform Requirements in 
Dispensing," L. E. Sayre makes some interesting observations. 
"If what is prohibited within a state is permitted beyond its borders, 



Am. Jour. Pharm. 
May, 1914. 



Current Literature. 



225 



tfre statutes of prohibition become not only inefficient, but most use- 
less. If what is prohibited within a drug store is permitted in a 
physician's dispensary, the law likewise becomes measurably inop- 
erative as far as the public is concerned." 

He makes the statement that such conditions exist and that in 
some of the different states the evil has been exposed. He quotes 
Mr. Roemer, who, at a meeting of the New York Pharmaceutical 
Association, made the announcement that an investigation of some 
of the medicines dispensed by physicians showed a sad state of 
affairs ; heroin tablets containing no heroin, morphine tablets with- 
out morphine, and elixir of terpin hydrate in which the terpin hydrate 
was conspicuous by its absence ! 

Mr. Sayre believes that the interest of the public could be safe- 
guarded by the state laws requiring all medicine dispensed by phy- 
sicians to bona fide patients to conform to legal standards, and, fur- 
ther, that any place where drugs are compounded, dispensed, or sold 
should be amenable to official inspection. 

If dispensing by medical men has resulted in conditions which 
are prejudicial to the public health — and from this standpoint alone 
should the question be viewed — then legislative regulation must, 
and no doubt will, be undertaken by the various states. This ques- 
tion is beginning to loom up as never before and must be settled 
sooner or later. It probably would be a good plan if the various 
state medical and pharmaceutical societies at their coming meetings 
for the year were to take hold and thresh this matter thoroughly and 
formulate some definite opinion upon the whole subject. 

John K. Thum. 

Chemical Examination of Dicoma Anomala. By Frank 
Tutin and William J. S. Naunton. The Wellcome Chemical Re- 
search Laboratories, London. 

The material employed for this investigation consisted of the 
entire air-dried plant of Dicoma anomala, Sond., obtained from 
South Africa. 

An alcoholic extract of the plant, distilled in a current of steam, 
yielded a small amount of an essential oil. The portion of the ex- 
tract which'was soluble in water yielded a small amount of a colorless 
crystalline glucoside, and a large amount of a yellow amorphous 
product, which, on hydrolysis with alkali, gave 3 : 4- dihydroxycin- 



226 Philadelphia College of Pharmacy. { Am ^\^ mi 

namic acid. The aqueous liquid contained, furthermore, a quantity 
of sugar which yielded d-phenylglucosazone, melting at 21 8°. 

The portion of the extract, which was insoluble in water, formed 
a dark-colored, resinous mass. It consisted largely of amorphous 
products, some of which gave 3 : 4-dihydroxycinnamic acid on hy- 
drolysis, and a small amount of an amorphous alkaloid was also 
present. The following definite substances were obtained from the 
resin : Hentriacontane C 31 H 64 ; a phytosterol C 28 H 46 ; palmitic, 
stearic, arachidic, cerotic, and melissic acids, together with some 
unsaturated acids which appeared to consist chiefly of a compound, 
C 16 H 30 O 2 , such as has been obtained by Bull (Ber., 1906, 39, 3537) 
from cod-liver oil. 

________ . J. K. T. 

PHILADELPHIA COLLEGE OF PHARMACY. 
Annual Meeting. 

The annual meeting of the Philadelphia College of Pharmacy 
was held March 30th, at 4 p.m., in the Library; the President, 
Howard B. French, presiding. Twenty-two members were present. 
The minutes of the quarterly meeting held December 29th, 191 3, 
were read and approved. The minutes of the Board of Trustees for 
December 2nd, 1913, January 6th, February 3rd and 9th were read 
by the Registrar, J. S. Beetem, and approved. 

President French delivered his Annual Address, when Mr. Ber- 
inger moved that the address be referred to the Publication Com- 
mittee, as there were many items of information that should be 
given to the public through The American Journal of Pharmacy, 
particularly the items referring to the instruction as given in the 
College. Seconded, and so ordered. (See p. 233 in this issue of this 
Journal.) 

Report of the Publication Committee was read by Professor 
S. P. Sadtler. The Journal has been published regularly during 
the past twelve months. The financial statement presented shows 
a creditable balance after paying all bills. It is impossible to supply 
a complete set, as some of the earlier volumes have one or more 
numbers missing. It is hoped that the sale of back numbers will 
increase so that a general index since 1890 can be published. There 
is need for such an index, as is shown by a number of inquiries for 



Am M™ r \gu ana -} Philadelphia College of Pharmacy. 227 

one, and even orders have been received. In discussing the report 
Mr. Beringer asked if it was possible to reprint the missing back 
numbers in order to supply complete sets. Professor Remington 
suggested making use of a photographic process, in place of printing, 
to replace back numbers, when Mr. England moved that in order to 
secure reprints of back numbers .the subject be referred to the 
Publication Committee, with power to act. So ordered. 

Report of Committee on Pharmaceutical Meetings. — Pro- 
fessor Kraemer said that the work done during the past few years 
has not been all it should be, owing to the fact that (as there are 
so many pharmaceutical societies in Philadelphia) there was a cor- 
responding division of energy. Yet there are some indications that 
our College may be able to come back to the work in the old spirit 
and with renewed vigor. In addition to the meeting last May, when 
the students of the graduating class presented abstracts of their 
theses, there have been three other meetings held. The first of these 
was in October, when Professor Eugene Charabot, of Paris, gave a 
charming address in French on " The Formation and Distribution 
of Odorous Products in Plants." This was rather a unique occasion 
in that a large number of students were present and nearly every 
one expressed delight in the privilege of hearing this discourse. The 
article was printed in full in the Journal, translation having been 
made. He also stated that he had just received a request from the 
editor of a Hungarian periodical to reprint the address. 

Another meeting was held in November. Professor La Wall 
had an article on the " Detection of Chicory in Decoctions of Chicory 
and Coffee." This paper caused a great deal of interest, and was 
published in full in the Journal. Mr. Boring exhibited several 
specimens of elixir of iron, quinine, and strychnine, and Professor 
Remington gave an illustrated lecture on " Some Pharmaceutical 
Celebrities I Have Met " ; also touching on the pharmaceutical col- 
leges and the professional aspect of pharmacy in Europe, especially 
England and Germany. 

The third meeting was held in February, when Mr. Lobeck 
gave a talk on " A Roughing Trip Across the Continent," illustrated 
with colored photographs. It was a very practical talk not only on 
how one should arrange a vacation, but to get the most out of it. 

Editor's Report, read by Professor Kraemer. During the past 
year we have published 572 pages, exclusive of a 10-page index. 
This matter included 75 original and selected papers covering a wide 



228 Philadelphia College of Pharmacy. { A %a°%iJ ar,n - 

range of subjects relating to pharmacy. We have received the 
support of investigators in various parts of the United States and 
those connected with other colleges ; our own members continue 
to contribute articles and in other ways promote the objects of the 
Journal. The following graduates have contributed articles during 
the year: George M. Beringer, George M. Beringer, Jr., Dr. Robert 
A. Hatcher, Victor O. Homerberg, Henry Kraemer, Professor 
Charles H. La Wall, Dr. Frederick B. Power, Sister Bertha Muller, 
Professor Joseph P. Remington, John R. Rippetoe, John K. Thum 
and M. I. Wilbert, and from the Honorary Members : Professor 
Charles E. Bessey, Professor W. G. Farlow, Professor A. Tschirch 
and Dr. A. L. Winton. 

The Quarterly Report on Progress in Pharmacy, by M. I. Wil- 
bert, continues to be one of the important features of the Journal, 
as it gives an excellent resume of discoveries of interest to medicine 
and important happenings in pharmacy. During the past year we 
have published a number of general articles which have given in a 
nutshell some of the advances in modern science. Among these 
articles we mention Ehrlich's Chemical Therapy, Phylacogens, Col- 
loids and Crystals, Enzymes, and Phenomenon of Catalysis. 

Curator's Report, read by J. W. England. The Museum of 
the College is growing yearly in importance. The entire collection 
of drugs and drug products and the Martindale Herbarium should 
be relabelled. The containers for the drugs should be standardized 
to two sizes only. The Museum could be made more valuable to the 
pharmaceutical public as a place of reference for standard or typical 
drugs and drug products, and most interesting also to the general 
public, if the historical collections were properly displayed. The 
Museum consists in large part of typical specimens of rare drugs. 
It should be improved by the addition of typical specimens of the 
more commonly used drugs as well, and especially by a proper dis- 
play of our historical matter and apparatus. 

The recommendations and suggestions in the Curator's report 
were, on motion, referred to the Board of Trustees. 

Librarian's Report, read by Professor Sadtler. During the 
year the Library has added by purchase, gifts, and exchanges a 
total of 105 volumes, 80 volumes of periodicals and theses have been 
bound, 2384 books have been accessioned, classified, and shelf- 
listed, making a total of 7264 books ready to be catalogued. Use 



Am Ma°y r i9i4 arm ' } Philadelphia College of Pharmacy. 229 

of Library during the year by 1375 persons, an increase of 378 over 
last year. 

The report of the Committee on Nominations was read and 
ordered, entered and filed. 

A communication was read from C. Carroll Meyer, declining the 
nomination for membership in the Board of Trustees because of 
pressure of business preventing his attendance at the meetings. 

The President appointed Professor F. X. Moerk, Mitchell Bern- 
stein and E. H. Hessler tellers, to conduct the election. The report 
of the Committee on Nominations being again read, the members 
proceeded to a ballot. While the ballots were being counted, Pro- 
fessor Stroup alluded to a recent notice received from the Fire 
Marshal and quoting an Act of Assembly prohibiting smoking in any 
part of the building. He hoped there would be some modification of 
the rule so as to permit smoking in the corridor, which was entirely 
fireproof. Past experience had shown that when prohibition was en- 
forced the entrance and the street in front of the College were used 
as a place for smoking and a number of complaints and police 
troubles had resulted. A number of the members related various 
experiences, viz., President French, Professors Remington, Kraemer, 
Sadtler, Lowe, Messrs. Beringer and Poley; the speakers generally 
thinking that, while protection from the risks of fire was absolutely 
necessary, some means should be devised to permit smoking in some 
part of the building. The discussion was closed by President French 
stating he would confer with Director Porter regarding the matter. 

The tellers reported the results of the election as follows : 

President, Howard B. French ; first vice-president, R. V. Matti- 
son, M.D. ; second vice-president, J. L. Lemberger; treasurer, Rich- 
ard M. Shoemaker; corresponding secretary, A. W. Miller, M.D. ; 
recording . secretary, C. A. Weidemann, M.D. ; curator, Joseph W. 
England ; editor, Henry Kraemer ; librarian, Katharine E. Nagle ; 
trustees for three years : Joseph P. Remington, C. Stanley French, 
George B. Evans ; Publication Committee : Samuel P. Sadtler, Henry 
Kraemer, Joseph P. Remington, Joseph W. England, Martin I. 
Wilbert, Charles H. La Wall, and John K. Thum; Committee on 
Pharmaceutical Meetings : Henry Kraemer, Joseph P. Remington, 
C. B. Lowe, George B. Weidemann, and E. H. Hessler. 

The President declared the above duly elected. 

The President made the following appointments : 



230 Minutes of Board of Trustees. { A % J a 7,\ 9 u. arm ' 

Committee on By-Laws : George M. Beringer, Joseph W. Eng- 
land, and C. A. Weidemann. 

Delegates to the Pennsylvania Pharmaceutical Association : C. 
B. Lowe, Joseph P. Remington, F. P. Stroup, O. W. Osterlund, 
William E. Lee, Charles H. La Wall, and E. Fullerton Cook. 

Delegates to New Jersey Pharmaceutical Association : Henry 
Kraemer, George M. Beringer, C. B. Lowe, Charles H. La Wall, and 
H. P. Thorn. 

Delegates to Delaware Pharmaceutical Association : A. W. Miller, 
M.D., C. B. Lowe, and H. J. Watson. 

The President announced the death of David H. Ross on Jan- 
uary 26, 1 9 14. He joined the College in 1888. 

William M. Morrison presented an old scale and two cases of in- 
struments originally owned by Dr. Stott, who died in 1837. The 
thanks of the College were tendered the donor. 

C. A. Weidemann, M.D., 

Recording Secretary. 



ABSTRACTS FROM THE MINUTES OF THE 
BOARD OF TRUSTEE'S. 

December 2, 1913. — Sixteen members present. 

Committee on Library reported total number of books accessioned 
to date 5449. A number of books were purchased during the month 
and the Library was used by 154 persons. 

A -communication from the Board of Public Education was read, 
recommending that Miss Florence McGarrity be awarded a scholar- 
ship ; and, on motion, the recommendation was approved. 

An application for active membership was received from a 
graduate of the 1913 class, now a resident of China, and, as usual, it 
was referred to the Committee on Membership. 

The Treasurer reported that on November 8th Mrs. Anna Shinn 
Maier sent her check for $2000 to establish a scholarship in memory 
of her father, James T. Shinn, the income from said amount to be 
devoted for scholarship purposes. On motion, it was voted that the 
Treasurer convey the thanks of the College to Mrs. Maier. 

January 6, 1914. — Fifteen members present. 

Committee on Property reported the change from white to green 



Am 'M J a°y r i9i4 ftrm ' } Minutes of Board of Trustees. 231 

shades in the electric light over the lecture table in the Materia 
Medica room. 

A petition signed by 75 per cent, of the students relative to the 
establishment of a lunch room in the College building was submitted 
by the Property Committee. The Dean explained in detail the 
reasons that prompted the presenting of the petition by the students, 
and advocated the adoption of a plan complying with their request. 
After some discussion it was moved that the Board approve the 
plan if the Committee on Property found that same could be put in 
operation without the College being compelled to assume any respon- 
sibility. It was so ordered. 

Committee on Library reported 476 books accessioned and shelf- 
listed during the month. A number of books had been donated and 
190 persons had used the Library during the month. 

Committee on Accounts and Audit reported they had examined 
the accounts of the Treasurer, Registrar, and the American Jour- 
nal of Pharmacy, and found them correct. 

Committee on Announcement reported the publication of the 
December issue of the Bulletin, that Pharmacy Talk No. 1 had been 
sent out, and that they had in preparation a series of 8 " Talks " — 
one to be issued each month. 

The Corresponding Secretary of the College read several letters 
from those who were recently elected to Honorary Membership in 
the College. 

The Committee on Membership having reported favorably on 
the application of Mr. Job Fong, of Canton, China, for active mem- 
bership, a ballot was taken and he was unanimously elected. 

February 3, 1914. — Fourteen members present. 

Committee on Property reported that inquiries had been made 
and it was found to be possible to make arrangements with a caterer 
to serve a light lunch in the College building for the accommodation 
of the students. On motion, the matter was referred to the Com- 
mittee on Property with power to act. 

Committee on Library reported that 454 books were accessioned 
during the month, making a total of 6378 books ready to be cata- 
logued. The Library was consulted by 143 persons. 

Committee on Instruction reported progress concerning matters 
that they had had under consideration. 

The Chair announced that Dr. P. S. Stout had been requested 
to present a report of the Alumni Special Committee having in 



232 



President's Address. 



Am. Jour. Pharm. 
May, 1914. 



charge the Centennial Fund, and asked that the regular order of 
business be suspended. This being agreed to, Dr. Stout was intro- 
duced and presented a detailed report of what had been done up to 
this time. The main object of the movement is to obtain by sub- 
scription and bequest, as may be most acceptable to the donor, a 
fund of $500,000 or more, to be devoted to improvements — location, 
building, equipment, etc., and to the establishment of an endowment 
for the College. The action of the committee was endorsed, and 
the Board gave assurance of furthering the movement in every way 
possible. ; : M i j Jul 

Committee on Examinations reported they had been engaged for 
several months in formulating a set of rules for regulating the con- 
duct of examinations in the College. A number of recommendations 
were submitted and extended discussion followed. As this was an 
important matter, it was voted that further consideration of the 
subject be deferred to an adjourned meeting to be held February 9th. 

The Dean presented the form of certificate which the Board had 
some months before referred to a Special Committee for considera- 
tion, covering special branches of study. The form met with 
approval, and it was voted that certificates be finished in accordance 
with the outlines proposed. 

An application for active membership was received and referred 
to the appropriate committee. 

February 9, 1914. — Eleven members present. 

This meeting was called to give further consideration to the re- 
port of the Committee on Examinations. After an extended dis- 
cussion, participated in by many of the members, action was deferred. 



PRESIDENT'S ADDRESS. 1 
To the Members of the Philadelphia College of Pharmacy: 

Your President has pleasure in submitting at this time, in ac- 
cordance with his established practice, a brief summary of matters 
of general interest relating to your institution. 

The College buildings at the present time are in good condition. 
The walls and ceiling of the library have been' painted, the floor 
covered with a cork carpet, and new chairs provided. The walls of 
the back stairway have been coated with a light-colored paint, 
which has proven of advantage in brightening up this portion of 

1 In abstract. 



Am. Jour. Pharm. 
May, 1914. 



President's Address. 



233 



the building. Alterations were made in the third-floor Microscopical 
Laboratory, giving greater facilities for the revised and expanded 
course in Bacteriology, which is now an obligatory course in charge 
of Prof. John A. Roddy. Changes have also been made in Alumni 
Hall for the benefit of the classes in Microscopy. 

Following the approval of the Board of Trustees of a petition 
signed by a number of the students, asking that a lunch-room be 
established, a lunch counter was started a few weeks ago and is 
being continued with increasing success. The lunches furnished 
are substantial and wholesome, and from the patronage received it 
would appear that the students in general appreciate the innovation. 
The Property Committee will, no> doubt, £nd it necessary, in the 
near future, to enlarge the facilities for this purpose, as the present 
accommodations are not equal to the demand. 

The total number of students in attendance at the College at this 
time is 434, an increase of fourteen over last year. Of the number 
mentioned, 145 are first-year students, 109 second-year students, 
141 third-year students, 38 special chemistry students, and 1 student 
taking the Food and Drug course. There were 168 first-year 
matriculants — 167 regulars and 1 special. Of this number, 1 student 
is deceased and 22 are not attending. The second-year matriculants 
numbered 113 — 112 regulars and 1 special. Of this number, 4 are 
not attending. There were 124 regular third-year matriculants and 
18 students remaining from class of 1912-13. Of the total of 142 
third-year students, 1 is not attending. 

Of those seeking admittance to the College at the beginning 
of the fall term, 29 applicants were not able to furnish satisfactory 
entrance credentials. These were given the privilege of remaining 
at the College and repeating the first-year work during 1914-15, in 
the meantime being expected to qualify. A few of the number have 
availed themselves of this privilege, but of these 'only four are 
attending at the present time, and under the circumstances are not 
listed as students. 

In the department of Analytical Chemistry, 13 first-year, 28 
second-year, and 35 third-year students have been doing special 
work. Of the number of third-year students mentioned, 9 are 
doing thesis work. Twenty-five students are taking the special 
laboratory course in Bacteriology; of this number, 7 are specials 
and 18 regulars. Fourteen of the special Chemistry students are 
availing themselves of the special course in Microscopy ; and 10 



234 President's Address. { Am 'Ma y, r i9 P i4 arm ' 

students are doing special work in the Microscopical Laboratory, in 
connection with their theses. 

The work in the Department of Pharmacy for the course of 
1914-1915 is being successfully carried on. 

The recording of the attendance, as now required by the State 
Pharmaceutical Board, has been of considerable value, and resulted 
in a higher -grade of scholarship being attained by the classes. 

The extra lectures on pharmaceutical subjects given during 
the college courses have been of material value and more largely 
attended. 

The course in Commercial Training, under the control of the 
Department of Pharmacy, and for which the students are not 
charged, has been greatly increased; the number of hours devoted 
to this branch has been doubled since last year. Illustrative 
material is fully shown, bookkeeping methods are compulsory, and 
students are now required to keep an individual set of books and 
submit them for examination. 

The Department of Botany and Pharmacognosy has given evi- 
dence of considerable advancement during the past year. A special- 
ized course in Microscopy has been developed, giving the special 
chemistry students enlarged opportunities for increasing their effi- 
ciency and broadening their powers as analysts. The course com- 
prises a series of laboratory periods on Saturday mornings and 
includes a wide range of topics, namely, the study of drugs, foods, 
and technical products with their deterioration and adulteration. 
The large number of specimens bearing upon this work, which your 
Professor of Botany and Pharmacognosy and his assistants have 
been diligently collecting for a number of years, is now being 
brought into practical use, and is proving of great advantage. 

It is of interest to note the increasing demand among agricultural 
experiment stations and the government laboratories for pharma- 
cognocists or thoroughly trained analysts ; and as microscopical 
courses are not, as a rule, included with chemical courses given in 
this country, the Philadelphia College of Pharmacy, in the establish- 
ment of such a course, will undoubtedly be enabled to prepare 
students of chemistry for a broader knowledge and a deeper under- 
standing of the intricacies of the work they have elected, thus 
extending the educational prestige of the College. 

The greenhouse and roof garden continue to furnish the students 
in Botany and Pharmacognosy facilities for growing plants and con- 
ducting special investigations. 



Am. Jour. Pharm. 
May, 1914. 



President's Address. 



235 



In the Department of Materia Medica the Physiological assay of 
drugs has been given increased attention, with good results. Your 
Medical Examiner reports that the physical examination of your 
students is somewhat hampered by lack of sufficient light. It may, 
therefore, be necessary for your Committee on Property to install 
a special light for this purpose in the near future. 

On Thursday evening, May 22, 191 3, the 92nd Annual Com- 
mencement exercises of your College were held in the Academy of 
Music. The graduating class numbered 123, representing 22 States 
of the Union, District of Columbia, Canada, China, and Russia. 

During the past year the College has received from Mrs. Anna 
Shinn Maier, daughter of your late treasurer, James T. Shinn, a 
sum sufficient to convert the Shinn Memorial into a scholarship. 

The Pennsylvania Scholarship Fund of $2500 is nearing com- 
pletion ; $2200 has been collected. 

There are at present 148 active members of your College, and 
13 associate members. During the year 6 active members and 1 
associate member were elected. The resignation of one active mem- 
ber was received; and your President regrets to report the death 
of three of your active members during the year, as follows : 

John W. Ridpath, May 8, 191 3. Joined the College in 1888. 

Evan T. Ellis, September 29, 1913. Joined the College in 1852. 

David H. Ross, January 26, 1914. Joined the College in 1879. 

It is of interest to note that Evan T. Ellis was the oldest member 
of the College. 

It is thought desirable by your President to bring to your atten- 
tion the fact that the Department of Public Safety of Philadelphia, 
recognizing the danger incident to smoking in buildings where 
people are assembled in numbers on various floors, deemed it 
necessary to send a communication to your College, reading as 
follows : 

Mr. Howard B. French, President, 
Philadelphia College of Pharmacy, 
145 No. 10th Street, 
Philadelphia. 

Dear Sir: 

Complaint has been made to this Bureau of the promiscuous smoking 
of cigarettes and cigars in the building of the College of Pharmacy. 

The Fire Marshal has made an inspection of the complaint and considers 
it of vital importance that the practice be discontinued at once. 



236 President's Address. { Am - J° a u y r ; 

I therefore request that proper notices be placed in all parts of the 
building where there are no tile or cement floors, in order that those offend- 
ing may have knowledge of the fact that it is in violation of the Act of 
Assembly. 

I would appreciate it if you would give this the publicity it deserves. 

Yours very truly, 

(Signed) Geo. D. Porter, 

Director. 

The body of this communication has been printed and promi- 
nently displayed throughout your buildings; and it is earnestly 
hoped that students in the College will respect said notice by dis- 
continuing the practice of smoking in the portions of the buildings 
where there are no tile or cement floors, and that arbitrary measures 
to enforce the order may not be found necessary. 

Your President wishes to call attention to the fact that on the 
21st of March, 1921, the College will have attained the one hun- 
dredth anniversary of its existence. This is but seven years away, 
and your President desires to urge upon all members of the College 
the desirability of collecting and placing in possession of the College 
any historical matters they may have or may be able to obtain. He 
would suggest that old prescription labels and labels referring to 
specific preparations could be readily collected from time to time 
from many of the old drug stores, and would prove of much interest. 
He also hopes that a strenuous effort may be made to collect 
as many of the old-time appliances as possible. It is the earnest 
hope of your President that when celebrating the 100th birthday 
of the College there may be an historical exhibition at that time that 
will not only attract the attention and interest of the pharmacists 
throughout the country, but of members of the medical and allied 
professions. 

In closing, your President desires to express appreciation to 
those of the officers and faculty who have so heartily cooperated 
with him during the past year; and to those who have not been 
in full accord with his views, he wishes to express the hope that 
all personal feelings may be put aside and that a united effort may 
be made to continue the prosperity and advancement of this institu- 
tion, which is dear to the hearts of all those associated with it. 

Howard B. French. 

March 30, 1914. 



Am. Jour. Pharm. 
May, 1914. 



The Vitamines. 



237 



THE VITAMINES. 1 

The Recognition oe Essential Constituents of the Diet 
Hitherto Unclassified — Deficiency Diseases. 

By Percy G. Stiles. 

If a physiologist is asked what are the requisites of a normal diet 
he will probably reply somewhat as follows : First, it must represent 
an adequate quantity of available potential energy, not less than 
2,000 calories for the average human adult. Second, it must contain' 
protein (nitrogenous) food sufficient to compensate for the un- 
avoidable daily loss of similar material from the body. Third, it 
must be palatable and digestible, making due allowance for personal 
idiosyncrasy. He will very probably content himself with these 
three postulates. 

If the inquiry is pressed the man of science may recollect that 
another necessary condition of successful nutrition is a proper 
supply of the inorganic or mineral elements in sufficiently varied 
assortment. The tissues cannot be developed or maintained without 
chlorides, phosphates, and other saline contributions. The need for 
substances of this class is more urgent during the period of growth 
than later, but it always continues to exist. A similar statement may 
be made with reference to the protein of the ration ; this, too, must 
be furnished in relative abundance and varied form during the 
growth of the subject and may be reduced when full stature has 
been reached. Mendel has shown that kind as well as quantity 
must be considered when protein is chosen for experimental nutri- 
tion of an animal. Proteins from certain sources suffice for main- 
tenance only and not to minister to growth. 

With the accumulation of physiological data during the past 
few years it has become increasingly apparent that there may be 
criteria for the adequacy of a diet not included in the list just given. 
There are now known to be organic compounds other than proteins, 
small quantities of which are absolutely essential to normal growth 
and even to continued health in the adult condition. The name of 
Vitamines has been proposed for all such substances. The word 
is well chosen in view of its root-meaning ; an amine is a nitrogenous 
compound of a certain type and a vitamine is obviously such a 



1 Reprinted from Science Conspectus, Vol. IV, 1914, pp. 10-13. 



2 3 8 



The V it amines. 



Am. Jour. Pharm. 
May, 1914. 



compound with the added distinction of being necessary to life. 
Casimir Funk of London has been one of the foremost contributors 
to the development of this conception and a valuable summary of 
his own work and his judgment of the work of others may be found 
in the Ergebnisse der Physiologie, Vol. XIII, pp. 124-205. (Wies- 
baden, 1913.) This article is the chief source of the present abstract. 

A class of serious disorders has long been known in which 
failure of nutrition could be named as the cardinal fact in the case 
and in which it has somewhat vaguely been assumed that the diet 
must be at fault. The most familiar disturbance of this class, at 
least to the general reader, has probably been scurvy. The chronicles 
of exploring expeditions in polar regions have contained many har- 
rowing accounts of the ravages of this disease. It has usually been 
associated with the consumption of a monotonous ration, deficient 
in fresh vegetables and often containing a great deal of salted or 
canned food. Certain supplementary articles of diet, such as onions, 
limes, and lemons, have been credited with some power to ward off 
or at least to mitigate the trouble and they have been spoken of 
as antiscorbutics. 

The victims of scurvy suffer from severe prostration, loosening 
of the teeth, intense soreness of the gums, friability of the bones, 
and a tendency to haemorrhage partly due to a loss of the coagulating 
property of the blood. Those who have read the classic journals of 
Doctor Kane will recall the distressing situation on board his ship 
at the end of the Arctic winter and the commander's device to 
cheer his helpless men in the forecastle by setting up a mirror to 
bring into their midst the first sunbeam from the southern horizon. 
Scurvy has become less common with better supplies of food avail- 
able for such parties, but it has been noted within a very few years. 

Another disorder which has lately attracted much attention is 
beri-beri. It has its recognized centre in the East, particularly in 
Japan, China, Indo-China, and the Philippines. Its occurrence in 
Newfoundland has recently been reported. Those who suffer from 
beri-beri are usually the very poor and, in the Orient at least, they 
are people who live chiefly upon rice. In Japan the disease has been 
nearly eliminated from the army and navy by providing more liberal 
and varied rations. The symptoms are complex, but they are in 
general such as can be referred to the impairment of the nerves, 
which is known to be the most prominent physical change. There 
is a period of declining weight and strength and this is followed by 



Am. Jour. Pharm. > 
May, 1914. J 



The Vitamines. 



239 



the development of a " multiple neuritis " with partial paralysis in 
both the motor and the sensory realms. 

Various theories have been held with regard to beri-beri. It 
has been believed to be an infectious disease because it so often 
affects a large number of people who are closely associated, as in 
a prison, a ship, or a laborers' camp. The fact was formerly over- 
looked that such companies share the same diet and that their 
trouble may well be due to that source. This is now accepted as 
proved. But when the decision is reached that something must be 
wrong with the food there are still two possible views to be con- 
sidered. Is the diet positively poisonous or is it merely insufficient? 
This question has been asked both with reference to scurvy and to 
beri-beri. It is not easy to answer it in such a way as to meet all ob- 
jections. Nevertheless, the tendency is toward the conclusion that 
it is the inadequacy rather than the toxic nature of the food which 
is to be held responsible in these and perhaps in other cases. 

It is proposed to call such failures of nutrition " deficiency 
diseases." It is assumed that the lack is of one or more of the 
specific substances already termed vitamines. The evidence in 
support of such a conception is especially convincing in the case of 
beri-beri. As long ago as 1897 it was discovered that rice which has 
been " polished " — that is, deprived of its pericarp or immediate 
husk — has a tendency to induce beri-beri and that the inclusion of 
the pericarp makes it entirely wholesome. It has been possible to 
confirm this in a striking manner by experiments on birds. If a 
fowl or a pigeon is restricted to polished rice as a diet it soon re- 
fuses to eat. If forced feeding is then resorted to it soon becomes 
pitiably weak and cannot long survive. The partial feeding is thus 
as surely destructive as absolute starvation. Post-mortem study of 
such birds shows marked degeneration of the nerves. The service 
of the pericarp may be conceived of in either of two ways. The 
polished rice may contain an active poison for which the husk pro- 
vides a natural antidote. The alternative is that the pericarp 
furnishes a necessary constituent of the nerve tissue, a vitamine, for 
want of which the nerve-fibres deteriorate. How hard it is to choose 
between these two views has already been suggested. 

Funk has been successful in his patient endeavor to isolate 
the vitamine the lack of which causes beri-beri. He has obtained 
from the pericarp of rice a number of fractions, only one of which 
has the remedial property. This appears to be a definite organic 



240 



The V it amines. 



Am. Jour. Pharm. 
May, 1914. 



body to which a formula can be assigned. It contains nitrogen but 
not phosphorus, an element which earlier workers had believed to 
be concerned. The vitamine can be separated from other foods 
than rice. Various animal tissues yield it and so do certain veg- 
etables. Any kind of food which contains the vitamine may be 
used to supplement a ration of polished rice with the result that it 
becomes sufficient for the maintenance of the animal. Yolk of egg 
and yeast are said to have the curative power in the highest degree. 

It is interesting to follow Funk's conjectures as to the systemic 
effects of the withholding of the invaluable vitamine. We know 
that in starvation the organs which cannot be spared are sustained at 
the expense of others. The heart and the nervous system have been 
found to keep their full weight to the last while tissues which are 
less necessary to the continuance of life are greatly reduced. Even 
the bones are levied upon to the extent of one-sixth of their mass. 
We may expect to see the same principle illustrated in the partial 
starvation which is at the root of any deficiency disease. 

So in beri-beri.it may be supposed that the vitamine which is 
absolutely essential to the normal nervous system is not. at first con- 
fined to that part of the body. The feeding experiments have given 
evidence that it is present in the muscles though rather scantily. 
It is to be expected that in the event of failure of a supply direct 
from the diet the muscles will be made to surrender their store of 
the vitamine to replace that which has been destroyed in the nervous 
tissues. If we are to think that the vitamine is essential to the 
muscles as well as to the nerves we shall anticipate that its with- 
drawal will result in a disintegration of the muscle .protoplasm 
quite out of proportion to the small amount of vitamine yielded to 
the preferred creditor. So for a while there will be loss of weight 
and strength but no marked nervous symptoms because the nerves 
are being kept in condition at the cost of a remorseless sacrifice 
of the other tissues. When the internal supply ceases to be suffi- 
cient the acute nervous effects are at once developed. 

It is the opinion of Funk that both beri-beri and scurvy are 
prevented by the liberal use of potatoes. Before this vegetable 
was introduced into Europe there were severe epidemics which are 
believed to have been outbreaks of scurvy. The suggestion that 
the potato should now be added to the food-supply of the eastern 
countries in which beri-beri is prevalent seems a wise one. But 
the fact is to be emphasized that almost any diet is free from ob- 



Am. Jour. Pharm. 
May, 1914. 



The Vitamines. 



241 



jection if it is reasonably varied. It is where poverty or some 
other compulsion is operative that nutritional disasters are likely. 

The condition of the body in scurvy is quite different from 
that in beri-beri and the missing compounds are probably some- 
what unlike. Some articles of diet may protect against both ; some 
may be specific for only one. Allied with scurvy are the disorders 
called ship beri-beri, infantile scurvy (Barlow's disease), and the 
experimental scurvies which can be produced in animals by limit- 
ing the intake to a few foods. Still other pathological states may 
be found to have a more or less similar basis. An attempt has 
been made to justify the claim that pellagra is a deficiency disease, 
but this is strongly contested. Abnormalities of early development 
such as rachitis (rickets) and, perhaps, later perversions of growth 
such as cancer may be connected with the lack of certain chemical 
constituents in the income of the body. ' At this point it may be in 
order to say that the diet itself may conceivably be ideal and yet 
there may be a failure to utilize the vitamines offered either because 
of a failure to absorb them or because of the premature decomposi- 
tion in the alimentary tract. 

A few years ago Crichton-Browne, an English authority, in 
passing an unfavorable judgment upon the dietetic standards of 
Chittenden and others called attention to the fact that the diet 
approved by them seemed to correspond closely with that of the 
very poor. The comparison was based upon fuel value and protein 
content. It is now possible to modify the statement that the two are 
precisely equivalent. The low diet of the New Haven school is an 
inclusive one, while that of the poor is of limited variety. A supply 
of the requisite minor bodies — vitamines, if we adopt the term — 
is much more surely to be relied on in the first case. 

Bunge, the Austrian physiologist, pointed out in 1901 that sugar 
is an unnatural food, in that it has been refined to the exclusion 
of all compounds but saccharose. Foods which are not deliberately 
prepared by industrial or domestic processes are always mixtures, 
however much one constituent may predominate. The teaching of 
Sylvester Graham in the first half of the nineteenth century that 
the foods offered by nature should not be separated into their in- 
gredients but taken in their entirety is frequently reechoed in our 
own day. In the light of studies like those of Funk it is apparent 
that there is a certain foundation for the idea that foods may be 
" denatured " either by discarding valuable fractions or by modes 



242 Pharmaceutical Meeting. , { Am, M J a y ur i 9 u arm - 

of preparation which destroy essential compounds. The fear that 
disturbances of nutrition from such causes threaten the American 
people as a whole may be dismissed, but it is interesting to have a 
new insight into a matter which under certain conditions becomes 
of pressing importance. 



PHARMACEUTICAL MEETING. 

At the third Pharmaceutical Meeting held February 20th, Mr. 
A. K. Lobeck spoke on " A Roughing Trip Across the Continent," 
showing about 150 colored slides. While the subject may have 
seemed remotely connected with pharmacy, yet, as Mr. Poley very 
well brought out in his remarks afterward, anything which will 
attract the pharmacist's attention to out-of-door life will be a benefit 
to him and tend to draw him away from his confined state of 
existence. 

Mr. Lobeck attempted throughout the story of the trip to inter- 
pret the natural scenery of the country. The origin of Niagara 
Falls, the fact that they are receding at the rate of 5 feet per year, 
the geological reason for the forms observed in the Garden of the 
Gods, and the explanation of the scenery around Horse Shoe 
Curve were some of the things dwelt upon. A summary of the 
trip was given showing in detail the distribution of the expenses and 
giving the average of expenses for each day. Exclusive of railroad 
fares it was shown that the average cost per day was 88 cents, this 
low average being accounted for by the fact that during the trip 
of 63 days, 27 days were spent camping or on ranches, either work- 
ing or under more hospitable circumstances. 



What is Sleep? In an article on " Sleep " Dr. Boris Sidis says : 
" Sleep is not a disease, not a pathological process due to the accu- 
mulation of toxic products in the brain or in the system generally. 
Sleep is not an abnormal condition, it is a normal state. Like the 
waking states, sleep states are part and parcel of the life-existence 
of the individual. Waking and sleeping are intimately related — they 
are two different manifestations of one and the same life-process — 
one is as normal and healthy as the other." 



THE PROCTER MONUMENT. PHOTOGRAPH OF MODEL OF THE BRONZE 
STATUE, DESIGNED BY EDWARD BERGE, AND TO BE ERECTED IN WASHING- 
TON, D. C, WHEN COMPLETED. 



THE AMEBIOAN 




JOURNAL, OF PHAEMAC 



Forty years have elapsed since the former editor of this Journal 
passed away on that fateful" night of February 10, 1874. During 
these forty years Pharmacy has developed by leaps and bounds ; new 
and weighty problems have arisen and have been solved, but many 
more remain, and the future gives promise of still greater achieve- 
ments in the profession which Procter loved. 

To John F. Hancock, of Baltimore, must be given the principal 
credit for inaugurating and carrying to successful fruition the work 
of erecting a statue in bronze to perpetuate the memory of this great 
pioneer in professional pharmacy. 

The ninety-seventh anniversary of his birthday was celebrated 
at the Philadelphia College of Pharmacy on May 3rd by a special 
meeting of his friends and former students. Reminiscences and 
tributes to his memory were freely uttered, followed by a dinner 
and a trip in the afternoon to Mount Holly, N. J., to visit his summer 
home and grave. Among those present were the following: 



JUNE, 1914 



PROFESSOR WILLIAM PRO' 



181 7-1874. 
By Joseph P. Remington. 



Dr. B. S. Erwin 
O. W. Osterlund 
C. A. Weidemann 
Dr. W. H. H. Githins 
Howard B. French 
J. S. Beetem 
W. Estell Lee 
Thomas D. McElhenie 
George M. Beringer 
Adolph W. Miller 



J. P. Remington 
Edward Berge 
J. F. Hancock 
Martin I. Wilbert 



C. B. Lowe 
C. H. La Wall 



R. C. Lippincott 
Otto Kraus 
Henry Kraemer 



F. X. Moerk 



(243) 



244 



Professor William Procter, Jr. 



Am. Jour. Pharm. 
June, 1914. 




Am. Jour. Pharm.i 
June, 1914. f 



Clayton French Fellowship. 



245 



Samuel M. Bines 
Hugh Campbell 
Dr. Henry A. Newbold 
Edwin M. Boring 



Dr. F. E. Stewart 
E. B. Jones 
Harry P. Thorn 
Alexander Dubell 



The special object of bringing Procter's friends together was to 
have them comment upon and criticise a model of a bronze statue 
which it is proposed to erect upon the grounds of the Smithsonian 
Institution, at Washington. The sculptor, Edward Berge, has re- 
produced in a remarkable manner, from photographs and very scanty 
material at command, a model which will serve as a starting point 
in the work of moulding the bronze statue. 

The following resolution was unanimously passed by the meeting : 
* 4 Resolved, That the work of Mr. John F. Hancock in connec- 
tion with the Procter Memorial be approved, and that the model 
and design of Mr. Edward Berge, of Baltimore, for the statue be 
accepted." 

It is meet and right to erect statues to our honored dead, lest 
we forget, but Procter's greatest monument must ever be his great 
services to Pharmacy, and especially his twenty-eight years as 
Editor of the American Journal of Pharmacy. 

" Could each here vow to do his little task as the departed did his 
great one — in the manner of a true man — not for a day, but for 
eternity ; to live as he counseled, not commodiously in the Repu- 
table, the Plausible, the Half ; but resolutely in the Whole, the Good, 
and the True." — Carlyle. 



THE "CLAYTON FRENCH FELLOWSHIP" IN THE 
PHILADELPHIA COLLEGE OF PHARMACY. 

When an institution is well equipped especially for doing work 
which is not in the regular routine of things it seems a shame when 
few or none are encouraged to profit by such favorable circum- 
stances. Our institution, owing to its long standing, the activity and 
friendly relations of its faculty with the outside world, has gradually 
accumulated apparatus and materials which, owing to the general 
nature of things, can be used only by those who are interested in 
problems external to the regular course of instruction. There is no 
such thing, as yet, as a post-graduate course here, but there has 
recently been made the first step in that direction. The fellowship 



246 



Clayton French Fellowship. 



Am. Jour. Phartil. 
June, 1914. 



which we are about to mention will make it possible for some 
capable and interested student to pursue work along .some particular 
line of investigation which would otherwise go untouched but for 
this stimulus. Both the student and the college will profit thereby, 
and there is also the chance that it may lead to some big benefit to 
the profession of pharmacy as a science. It is a hard enough thing 
to settle down to the prosaic task of fathoming out a difficult prob- 
lem, and anything like this which makes it an honor and which re- 
duces also the financial burden of such a task is almost essential to 
the building up of a great work. 

In order to provide for fellowships, and that those who would 
contribute to such endowments might know to what purposes they 
would be applied, a new article on Scholarships and Fellowships 
has been incorporated into the By-laws of the Philadelphia College 
of Pharmacy. This article reads as follows : 

" Scholarships and Fellowships covering instruction given in the 
College or studies pursued elsewhere by direction of its Board of 
Trustees, may be established by the Board of Trustees as funds for 
such purposes are provided. 

" To found a Pharmacy Course Scholarship, a sum of not less 
than $3000 shall be paid to the College. The student to whom such 
scholarship is awarded shall receive free instruction in all of the 
lectures and laboratories in the course leading up to a degree in 
Pharmacy for the period for which the award is made. 

" To found a Special Scholarship or a Partial Pharmacy Course 
Scholarship, a sum of not less than $1500 shall be paid to the Col- 
lege. In no case shall the sum paid be less than, when invested, will 
produce an income equivalent to the fees required by the College 
from students for similar instruction. The donor may designate 
the course of lectures or laboratory instruction to which such special 
bequest or donation is to be applied. The student to whom such 
Special Scholarship or Partial Pharmacy Course Scholarship is 
awarded shall receive free instruction in the lectures and laboratories 
named for the period for which the award is made. 

" To found a Research Fellowship, a sum of not less than $5000 
shall be paid to the College ; the income from such a foundation is to 
be paid to the student to whom such fellowship is awarded to pay for 
the tuition, materials, and apparatus used in the research work and 
as compensation for such aid in the laboratories, museums, library, 
or other department of the College as the recipient may render. 



Am. Jour. Pharm. 
June, 1914. 



Clayton French Fellowship. 



247 



" The founder of a fellowship may designate the title of the 
fellowship and the special investigation, science, or department to 
which the research is to be directed, and may select, from time to 
time, the fellow to whom the fellowship is to be awarded. In the 
absence of such designation or selection the Board of Trustees shall 
decide the title and the application of the research, and, subject to 
confirmation by the Board of Trustees, nominate from time to time 
the fellow on written application setting forth the subject of re- 
search work that is to be engaged in, preference is to be given to 
post-graduate study in the sciences associated with pharmacy. 

" If any student to whom a scholarship or a fellowship is awarded 
is found to be of improper character, or is deficient in mentality or 
scholarship, or fails to attend the instruction or to pass satisfactory 
examinations, the award shall be cancelled. 

" A scholarship or a fellowship is awarded, in accordance with the 
By-Laws and Rules and Regulations established by the Board of 
Trustees, to the student named and for the period specified and can- 
not be transferred by the recipient. 

" All moneys received by the College for the purpose of founding 
a scholarship or fellowship shall be invested by the Finance Com- 
mittee in accordance with their best judgment, and a separate 
account shall be kept of each such scholarship or fellowship. 

" If any donation or bequest received for the purpose of founding 
a scholarship be insufficient for the purpose intended, then such sum 
received shall be invested by the Finance Committee, and when the 
aggregate of the principal and accrued interest is sufficient for the 
purpose intended, the scholarship shall be established by the Board of 
Trustees. 

" The Board of Trustees shall have authority to offer, in the 
name of the College, free scholarships to students of such public 
schools or other educational institutions as the Board may designate." 

At a recent meeting of the Board of Trustees President French 
announced that Mrs. Mary French Banks, of Philadelphia, had 
donated through him the sum of $5000 for the establishment of a 
fellowship as a memorial to her father, Clayton French. The Board 
gratefully accepted the sum and established a fellowship, to be 
known as the " Clayton French Fellowship." The -following is a 
copy of the letter of transmittal to Mrs. Banks by the Chairman of 
the Board of Trustees: 



248 



Clayton French Fellowship. 



{ 



Am. Jour. Pliarui. 
June, 1914. 



May 5, 1914. 



Mrs. G. W. Banks, 
Philadelphia, Pa. 

Dear Madam: 

Mr. Howard B. French, at the meeting of the Board of Trustees 
of the Philadelphia College of Pharmacy this p.m., presented your 
check drawn to his order and endorsed by him to the Treasurer of 
the College for $5000 to establish a Fellowship as a memorial to 
your deceased father, Clayton French. Permit me to assure you 
the appreciation of the Board for the courtesy you have extended 
and the honor that you bestow upon one who many years ago was 
a student in this institution. 

The following resolutions were unanimously passed and ordered 
to be forwarded to you : 

" Resolved, That the Board of Trustees of the Philadelphia Col- 
lege of Pharmacy gratefully acknowledge receipt of Five Thousand 
Dollars ($5000), through the hands of Mr. Howard B. French, from 
Mrs. Mary F. Banks, to be used in establishing a Fellowship in honor 
of her deceased father, the late Clayton French. 

" Resolved, That a marble tablet be erected in the hallway of 
the College, bearing the following inscription : 



" Resolved, That the Five Thousand Dollars ($5000) donated 
for establishing the Clayton French Fellowship shall be invested in 
our mortgage account, and that the income therefrom shall be used 
for advanced research work." 

Assuring you the deepest appreciation of the Board, I have the 
honor to be 



1824 



1890 



Clayton French 



FELLOWSHIP 



Established by his daughter 
Mary French Banks 
May 16th, 1914 



Yours truly, 



George M. Beringer, 
Chairman of the Board. 



Am 'jir e r 'i9i h r m '} Volumetric Estimation of Sulphates. 249 



THE VOLUMETRIC ESTIMATION OF SULPHATES. 
By Horace North. 

Although S0 4 is easily the most important acidic ion concerned 
in the operations of industrial chemistry, there is at the present time 
no satisfactory method of general application for its volumetric 
estimation. A method is proposed which, in the light of numerous 
experiments, promises to be widely useful. Subject to certain limita- 
tions which will be considered in due course, the method is applicable 
in the presence of the ions Li, Na, K, NH 4 , Cu -, Mg, Ca, Sr, Zn, 
Cd, Hg-, Al, Ni, Co, CI, P0 4 , B 4 7 . All data are referred to one 
standard solution which is readily prepared of exact strength and 
which is permanent. The end point of the titration is clearly defined. 
When all is in readiness an estimation requires fifty minutes. 

In 1877 Hinman 1 proposed to determine sulphuric acid as fol- 
lows : To a slightly acid solution of a sulphate heated to boiling 
is added a small excess of a solution of barium chromate in hydro- 
chloric acid, barium sulphate is precipitated, then the solution is 
neutralized with ammonia which precipitates the remaining barium 
chromate, the precipitates of barium sulphate and chromate are 
filtered off, and the chromic acid, determined in the filtrate by 
means of stannous chloride, is equivalent to the sulphuric acid in 
the original solution. 

This method is limited in its application ; in particular, metals 
forming chromates insoluble in the presence of ammonia as well as 
phosphates and borates interfere. Various modifications 2 designed 
to correct its inherent defects have been suggested without, however, 

1 Amer. Journ. Science and Arts, 114, 478. 

2 Andrews, Am. Chem. Journ., 2, 567; 32, 476-480. 

Marboutin and Molinie, Bull. Soc. Chim., 17, 950-955 ; 19, 713-717. Journ. 
Soc. Chem. Ind. (1897), 1041; (1898) 874. 
Reuter, Chem. Ztg. (1898), 357. 
Telle, /. Pharm. Chim., 7, 165-170. 
Bruhns, Z. anal. Chem. (1906), 573. 
Komarowsky, Chem. Zcit., 32, 770. 
Mitchell and Smith, Chem. Soc. Proc, 25, 291. 
Repiton, Monit: Sclent., 24, 382-384. 

Holliger, Stahl u. Eiscn, 30, 1376-1378; Z. Anal. Chem., 49, 84-93; 
angew. Chem., 22, 436-449. 

Roemer, Z. Anal. Chem., 49, 490-492. 



250 Volumetric Estimation of Sulphates. { Am -j^J; 

extending its usefulness. Thus, it having been shown that HC1 is 
oxidized on prolonged contact with Cr 2 7 , the strength of the stand- 
ard solution being thereby altered, trichloracetic acid was proposed 
to hold the BaCr0 4 in solution. In any case it is impossible to pre- 
cipitate BaS0 4 in the presence of chromate without coprecipitation 
of the latter in some degree. For this reason and in order, further, 
to avoid the uncertainty arising from the instability of solutions of 
barium chromate, some authors recommend separate solutions of 
barium and chromate, the, BaS0 4 being precipitated before the in- 
troduction of the chromate. Another way of avoiding the instability 
of acid solutions of barium chromate is to employ a mechanical 
suspension or cream of the salt. This idea would not seem to be in 
accord with good volumetric practice. Calcium carbonate has been 
used in place of ammonia, though with no very obvious advantages. 
Various means have been adopted for the estimation of the Cr 2 7 . 

The volumetric solutions required in the proposed method are : 

Normal Potassium Bichromate. — Dissolve 49.033 gms. 3 
K 2 Cr 2 7 , previously powdered and dried at 120 C, in sufficient 
water to measure 1000 c.c. 

The solution is normal with respect to oxidizing power. 

Tenth-normal Sodium Thiosulphate. — Measure 10 c.c. n/i 
KXr,C) 7 into a 100 c.c. glass-stoppered volumetric flask and make 
up to the mark. Measure 20 c.c. of this solution into a 500 c.c. 
Florence flask containing 1 gm. KI just previously dissolved in 
20 c.c. dilute sulphuric acid (100 c.c. cone. H 2 S0 4 + 900 c.c. water), 
rinse down the sides of the flask with 60 c.c. water, mix the liquids, 
cover the flask with a watch-glass and let stand six minutes. Dilute 
the liquid with 150 c.c. water and titrate the free I with a solution 
of sodium thiosulphate (25 gms. Na 2 S 2 3 + 5H 2 in 1000 c.c), 
adding starch indicator near the end. Divide 20,000 by the number 
of c.c. required and dilute each litre of the Na 2 S 2 3 solution to the 
volume indicated. 

The above is essentially the method of Seubert and Henke 4 for 
the iodometric estimation of Cr 2 7 . 

Third-normal Barium Chloride. — The solution is equivalent to 
the dichromate solution and contains 40.72 gms. BaCL + 2FLO per 
litre. 



3 The international atomic weights for 1913 were used throughout the 
investigation. 

4 Zeit. f. ang. C, 1900, 1147; " Volumetric Analysis," Sutton, 1904, 184. 



Am * /me,' i9i4. rm ' } Volumetric Estimation of Sulphates. 251 

Measure 4 c.c. HQ (sp. gr. 1.12), 40 c.c. water and 10 c.c. 
barium chloride solution (about 43 gms. BaCL + 2HLO in 1000 c.c.) 
into a 100 c.c. glass-stoppered volumetric flask, heat the liquid to 
boiling, run in 10 c.c. n/i K 2 Cr 2 7 , rinse down the neck of the 
flask with 10 c.c. water and without further heating add drop by 
drop with constant shaking a mixture of 15 c.c. ammonia water (sp. 
gr. 0.98) and 2 c.c. 36 per cent, acetic acid. Cool the mixture to the 
normal temperature, make up to the mark and filter with the aid of 
suction through an asbestos felt previously formed in the usual man- 
ner, then dried at about no° C. Titrate 40 c.c. of the filtrate under 
the conditions specified in the standardization of the n/io Na 2 S 2 3 , 
except that 40 c.c. water are used in place of 60 c.c, the total volume 
of the solution during the six-minute period of standing being 
100 c.c. Divide 20,000 by the number of c.c. n/io Na 2 S 2 O a re- 
quired, and dilute each litre of the BaCL solution to the volume in- 
dicated. A new trial is then to be made with, if necessary, the 
slight readjustment required. 

An estimation of S0 4 is carried out as follows : 

Transfer the sulphate solution containing about 0.16 gm. S0 4 to 
a 100 c.c. glass-stoppered volumetric flask, dilute to a volume of 
30 c.c, add sufficient HC1 (sp. gr. 1.12) so that the total amount, 
present is 4 c.c (if acidity is unknown, first neutralize with am- 
monia), heat the liquid to boiling, run in 20 c.c N/3 BaCl 2 , again 
heat to boiling, run in 10 c.c. n/i K 2 Cr 2 7 , rinse down the neck of 
the flask with 10 c.c. water and without further heating add drop 
by drop with constant shaking a mixture of 15 c.c ammonia water 
(sp. gr. 0.98) and 2 c.c. 36 per cent, acetic acid. Complete the 
experiment as specified under the standardization of the N/3 BaCl 2 . 

C.c. n/io Na 2 S 2 3 required X 0.008 = gm. S0 4 originally taken. 

The reaction between equivalent solutions of K 2 Cr 2 7 and 
BaCL is -expressed by the equation : K 2 Cr 2 7 + BaCL + H 2 = 
BaCr0 4 + K 2 Cr0 4 + 2HCI. The resulting HC1 retains in solu- 
tion a considerable portion of the Ba. On neutralizing with am- 
monia all of the Ba is thrown out as chromate and half the Cr 
originally taken remains in solution. 

A large number of preliminary experiments, the details of which 
it is hardly necessary to give, demonstrated the following points : 

(1) When cold solutions of K 2 Cr 2 Q 7 and BaCL are mixed and 
neutralized, the precipitate of BaCrQ 4 carries down soluble chro- 
mate in considerable and variable amounts. 



252 Volumetric Estimation of Sulphates. { Am 'jun7i9u rm ' 

(2) The same error in less degree occurs when the BaCl 2 solu- 
tion is added to the diluted and boiling K 2 Cr 2 7 solution and the 
neutralization effected at the boiling point. 

(3) The error is eliminated only when the K 2 Cr 2 7 and BaCl 2 
solutions are mixed in the presence of sufficient HQ to prevent the 
precipitation of BaCr0 4 , and then ammonia water is added drop 
by drop to the hot liquid ; further, the ammonia water must be fairly 
dilute so that not too much BaCr0 4 is thrown out at once as the 
liquid approaches neutrality. 

Acetic acid is unaffected by dichromate under the conditions of 
the procedure. 10 c.c. n/i K 2 Cr 2 7 were measured into a 100 c.c, 
volumetric flask, 40 c.c. water and 1 c.c. 36 per cent, acetic acid 
were added, the liquid was boiled 1 minute, cooled and made up to 
the mark. 20 c.c. required 19.95 c.c. n/io Na 2 S 2 3 . An inde- 
pendent experiment done in the same manner required 20 c.c. n/io 
Na 2 S 2 3 . 

The use of acetic acid widens the application of the method 
greatly. Numerous chromates insoluble in the presence of am- 
monia readily dissolve in acetic acid. The latter also permits of the 
application of the method in the presence of borates and, especially, 
of phosphates in limited amounts. It is highly important that the 
excess of acetic acid be not much greater than 0.5 c.c, which is nearly 
equivalent to 10 c.c. n/i K 2 Cr 2 7 . An undue excess would exert 
a marked influence on the solubility of the BaCr0 4 .and lead to too 
high results. 5 The quantities of reagents specified are such that 
under the actual working conditions of the procedure the excess of 
acetic acid finally present is close to 0.5 c.c. 

The method being designed for technical use, the volumes re- 
quired to be handled are kept within moderate limits. 

In the volumetric standardization of the BaCL under the con- 
ditions specified various errors compensate each other so perfectly 
that gravimetric assays show very nearly theoretical results. Ob- 
viously this fact is of the highest importance in the practical opera- 
tion of the method. If this were not so it would be necessary to 
standardize the BaCL gravimetrically and apply a correction to the 
titration. In the course of the work two independent sets of reagents 
were prepared. First lot of BaCL : 10 c.c. yielded 0.3885 gm. BaS0 4 , 

5 Cf. Bray, " A System of Qualitative Analysis for the Common Ele- 
ments," /. Am. Ch. Soc, 1909, 611-637. 



Am june, r 'i9 P i4 arm '} Volumetric Estimation of Sulphates. 25$ 

equivalent to 0.4066 gm. BaCL + 2H 2 0. Second lot of BaCl 2 : 
10 c.c. yielded 0.3886 gm. BaS0 4 , equivalent to 0.4067 gm. BaCL 
+ 2H 2 0. Theory demanded 0.4072 gm. BaCL, + 2H 2 Q. Error 
= 0.1 per cent. 

Ordinarily about 0.16 gm. S0 4 should be taken. If, however, 
the proportion of SC 4 is so small that 0.16 gm. cannot be taken 
without increasing unduly the concentration of the other ions, it is 
necessary to take into account the error arising from the solubility 
of the BaCr0 4 , which, under the conditions, is represented by 0.3 c.c. 
n/io Na 2 S 2 3 per 40 c.c. of the filtrate. For example, 10 gms. 
table salt were dissolved in sufficient water to measure 100 c.c. 
Volumetric and gravimetric estimations were made on 10 c.c. 
portions. 40 c.c. of the filtrate required 1.1 c.c. n/io Na 2 S 2 ;r The 
correction having been deducted, 0.0064 gm. S0 4 was indicated. 
BaS0 4 found: 0.0152 gm., equivalent to 0.0062 gm. S0 4 . 

Table I presents a large part of the experimental data and is self- 
explanatory. 

Notes Supplementary to Table I. 

a. Carefully recrystallized and dehydrated by gentle ignition; purity also 
established gravimetrically in the course of some previous work. 

. b. Cu- does not interfere, provided care is taken to prevent the premature 
formation of cuprous salt. Should this occur, the titrating fluid becomes 
cloudy. Shaking and standing may clear it. The n/io Na^S-Oa should be 
added in small portions with vigorous shaking. The first disappearance of 
the blue color is taken as the end. The titration may also be carried out 
without starch indicator, the thiosulphate being run in until there is no further 
change in color and the liquid acquires a slight permanent opalescence. 

c. Mg occasions a positive error variable between 1 and 2 per cent. The 
substitution of caustic soda for ammonia does not reduce this error. 

d. Two independent experiments. 

e. Although SrCrCXt is readily soluble under the conditions of the pro- 
cedure, the slight solubility of SrSOi greatly limits the application of the 
method in the presence of Sr. 

/. Less the correction 0.3 = 2 c.c. 

g. The salt was badly effloresced. 

h. The study of this element led to the addition of the ammonia and 
acetic acid mixed. Alumina once precipitated by ammonia redissolves with 
great difficulty in so weak an acid as acetic. Further, precipitated alumina 
occludes soluble chromate. Under the conditions of the procedure the 
aluminium remains in solution or, at most, the liquid becomes slightly 
opalescent. 

i. The usual formula with 7H2O was assumed; hence the weight taken. 
The salt actually contained 6H2O. 



Volumetric Estimation of Sulphates. {^jS^iSS^ 



C u 

<-> u 



OOOOhhmhN 

I +++++++ 



00 

-t- 

6 
+ 



N _ HOC 

6 6 6 m w 
++++++ 



a a a s a a 




a 


bX) bX) bX) bX) bX) bX) 




to 


rj- M Om-h O 






t>» O ONOO On O 


















6 6 6 6 6 6 




6 



a a a a a a a 

bx) bX) bx> bX) bX) bX) bX) 
O lO h ^) N P) N 

O hH M 1-1 HH M M 

6 6 6 6 6 6 6 



a a a a a a • 


• a 


be bjo bx) bx> bxi oa ; 


bX) 






M r-^o vO 00 . 




00 00 00 00 00 00 . 


! o . 


fOfOfOfOfOfO 




6 6 6 6 6 6 • 


6 



a a a a a a a 

be be bX) be bO OX) bx> 

i-i O O lO >0 ro O 

^ O fOOO 00 hoO 

6 6 6 6 6 6 6 



aaaaaaaaa 

bX)bX)bX)b£ibX)bX)bX>bX)bX) 



a a a a a a a 

bX) bX) bo bx> bXI bXi bX) 



6 


O oo \D \D ^oo 


4 Tt" <N 


00 


O no 


NOO O 


o 


CO 


O \D Q\ On O O 






*0 1-H 


ON00 o 


o» 00 


O 'O iO lO^O o 




<o 














O i-i 








o o o o o o 


o o o 


o 


o o 


o o o 


o o 


O 

00 


. 6 6 6 T) . 








. 6 






. " d d 6 V 


6 6 6 


6 


6 


9 d . 


d d 






odd 


6 


°. 6 




d d 


o 


o on on q w 


fO 




° c 


rt-00 O 


1O00 




O On ON On O O 


6 6 6 






ci On C 




"7 ^ 


M h h h N N 


Ol 






M h N 


<N l-H 



q q q q q q q 
6 6 6 6 6 6 6 
o o o o o o o 



q q q q q q q 
d d d d d d d 
o o o o o o o 



o 
tn 

d 
d 
O 

+ 

o 

CO 

O 

01 



.a 2 Sd^c^. 

oiw . in in in in 

a a a a a a a 

bX) bx> bxi bX) bX) bX) bX) 

vO O <OOnO o o 
ON 00 n ii O hh 

' 4 



q 
d 
o 

d 2 

8. a 

CO 



rB d-t" 

bX)^^ 



K oo ^ 
SOS 

CS3 r*>< 



sit 



in w in in m w 

a a a a a a 

bx> bxi bX) bX) bxi bX) 

PI lO^t CO^O O 
O^NIOOOOOO 

4- 4 t}- 



Ata :i,me r i9H arm '} Volumetric Estimation of Sulphates. 2$$ 

Phosphates.— 0.5 gm. NaJiPQ 4 +12ILO, 4 c.c. HQ (sp. gr. 
1. 1 2), 40 c.c. water and 10 c.c. N/3 BaCL, were mixed in a 100 c.c. 
flask, the liquid was heated to boiling, 20 c.c. water were added, then 
drop by drop with constant shaking a mixture of 15 c.c. ammonia 
water (sp. gr. 0.98) and 2 c.c. 36 per cent, acetic acid was added. 
Near the end a considerable amount of precipitate appeared which 
failed to redissolve on shaking or boiling. There was much phos- 
phate still in solution. Various other amounts of phosphate were 
tried under the same conditions. The results are given in Table II. 

Blank tests were done in the presence of various amounts of 
phosphate. The results are given in Table III. 



Table II. 



Na 2 HP04+ 12H2O taken 


Precipitate 


0.5 gm 


Considerable. 


0.3 gm 


Small. 


0.25 gm 


Slight. 


0.2 gm 


Slight. .. 


0.15 gm 


Barely visible. 


0.1 gm 


None. 



Blank tests were done in the presence of HgCL (0.45 gm. ) and 
Na 2 B 4 7 + 10 H a O (0.5 gm.), respectively. Neither substance 
interfered. 

Table III. 



Na 2 HP04 + i2H 2 taken 


N /io Na2S2 ° 3 required 


Per cent, error 


0.5 gm. 


21.3 C.C. 


+ 6.5 


0.3 gm. 


20.6 C.C. 


> +3- 


0.25 gm. 


20.3 c.c. 


+ 1.5 


0.2 gm. 


20.3 c.c. 


+ 1-5 


0.15 gm. 


20.05 c ' c - 


+0.25 


0.1 gm. 


20 C.C. 






Iron. — Fe- is, of course, inadmissible. Fe -, if present in the 
final titration, liberates I from KI and vitiates the result. Fe - • 
may be completely removed from the solution as basic ferric acetate 
by boiling the liquid after adding the mixture of ammonia and 
acetic acid. Unfortunately coprecipitation of soluble chromate 



8 By blank test is to be understood a test in which equal volumes of the 
KjO^Ot and BaCb solutions are taken, as in the standardization of the BaCb. 



256 The Patent Medicine Problem. (Am Jour pim™. 

^ \ June, 1914. 

occurs. The error is therefore negative and is too considerable to 
be neglected even in rough work. For example, the error in an 
experiment on ferric alum [FeNH 4 (S0 4 ) 2 + 12FLO] amounted to 
— 8 per cent. 

Chromium, — A large number of experiments was done on 
chrome alum. The results were much too high and very erratic. 
Indications pointed to the formation of chromous salts. 

Analytical Department, Lehn & Fink, New York. 



THE PATENT MEDICINE PROBLEM. 1 
By M. I. Wilbert, Washington, D. C. . 

The patent medicine problem, as it presents itself to American 
pharmacists to-day, is neither novel nor popular, and its continued 
growth has long since been recognized as a menace to> the devel- 
opment of pharmacy as a .desirable occupation. The business itself 
has developed as the joint off spring of cupidity and credulity and 1 
from a very early period has been the one object regarding which 
members of the various branches of the drug trade have differed 
on more frequently and more widely than on any other. 

While it is generally recognized that the manufacture, sale and 
use of so-called patent medicines should be considered primarily 
as a public health problem, the business from the drug trade point 
of view also involves economic questions which cannot well be 
ignored and which have, at times at least, quite overshadowed all 
public health considerations. That the economic feature of the 
problem is on the increase rather than decrease is evidenced by an 
editorial in the National Druggist (1912, v. 42, p. 414) which asserts 
that the number of establishments engaged in the manufacture of 
patent and proprietary medicines in 1899 was 2 > r 54> an d in 1909 
was 3,642. The value of the products at the factories in 1899 was 
$88,791,000, and in 1909 was $141,942,000, an increase of approxi- 
mately 70 per cent, in ten years. 

Whether the public health or the economic side of the problem 
is to be given the preference in the near future is a question that is 
well worth considering, and one which by the recent action of the 



1 Presented at a meeting of the City of Washington branch of the Amer- 
ican Pharmaceutical Association, February 18, 1914. 



Am 'junri9i h 4 arm '} The Pa tent Medicine Problem. 257 

American Pharmaceutical Association is once more set squarely 
before the American pharmacists for reply or action. 

The patent medicine problem as it is now before the members of 
the American Pharmaceutical Association for discussion, was out- 
lined in an editorial by the general secretary of the Association, in 
the Journal for April, 1913 (pp. 425-428). This editorial points out 
that the duty of the pharmacist to himself and to the public, in 
connection with patent medicines, is to define if possible the legiti- 
mate status for remedies of this kind, and to differentiate between 
acceptable and non-acceptable preparations. 

This proposition was presented to the Council of the American 
Pharmaceutical Association at the Nashville meeting, and after 
considerable discussion it was agreed to> appoint a Commission on 
Proprietary Remedies to consider the following general propositions : 

" 1. To inquire into and report to the Council from time to time 
upon the general subject of proprietary medicines, in their relations 
to pharmacy, medicine and the public health. 

" 2. To inquire whether any of the proprietary medicines, com- 
monly -known as patent medicines, contain alcohol or narcotic drugs 
in sufficient amount to render them liable to create a drug habit, or 
to satisfy such habits where otherwise created. 

"3. To inquire whether, or to what extent, the commonly adver- 
tised patent medicines contain potent drugs in sufficient amount to 
render them dangerous in the hands of the laity. 

" 4. To inquire into the extent to which ^patent medicines are 
fraudulently advertised, or differ in properties or origin from the 
claims made for them, and the extent to which they are advertised 
for the cure of diseases generally recognized by the medical science 
as at present being incurable." (7. Am, Pharm. Assoc., 1913, v. 2, 
p. 1195.) 

As the Commission has, so far as known, made no report to the 
Council of the American Pharmaceutical Association, there is, as 
yet, no indication as to what will or will not be the attitude of this 
Commission toward the preparations now on the market or to be 
marketed in the future. Some idea of the stand that must be taken 
by the members of the Commission if they desire to> make for 
progress rather than retrogression is evidenced by what has already 
been accomplished, not alone by the American Pharmaceutical Asso- 
ciation, but also by other related organizations, particularly the 
American Medical Association. 



258 The Patent Medicine Problem. { Am ; Tl me r "i9i h 4 arm ' 

Not to go too extensively into the history of the agitation re- 
lating to the manufacture and sale of patent medicines, more popu- 
larly designated as nostrums, we may well confine ourselves to the 
published records of the two national associations directly interested : 
the American Pharmaceutical Association and the American Medical 
Association, both organized somewhat over sixty years ago. 

The American Medical Association almost annually, from the 
time of its preliminary meeting in the city of New York, in 1846, to 
its reorganization at Saratoga Springs in 1902, adopted resolutions 
condemning nostrums and secret remedies of all kinds, and pointed 
out objectionable features connected with them. Previous to* the 
reorganization of the Association on the present basis, however, 
little or nothing of practical value was accomplished. 

The American Pharmaceutical Association has also devoted con- 
siderable time and space to the discussion of problems connected 
with the manufacture and sale of patent and proprietary remedies. 
A cursory review of the proceedings of the Association suggests the 
rather interesting fact that this agitation appears to have developed 
in cycles and to have been markedly acute in decennial waves, the 
maximum height of the agitation being evidenced in the early years 
of the decennium. Thus, beginning with the Proceedings for 1853, 
the second meeting of the Association, we find the following reso- 
lution, which was, on motion of Joseph Laidley, substituted for one 
previously offered by C. B. Guthrie, and adopted by a majority of 
the members present! 

" Resolved, That the American Pharmaceutical Association be- 
lieves that the use and sale of secret or quack medicines is wrong in 
principle and is in practice attended with injurious effects to both 
the profession and the public at large, and believes it to be the duty 
of every conscientious druggist to discourage their use. 

" Resolved, That this Association earnestly recommend to our 
pharmaceutical brethren to discourage by every honorable means 
the use of these nostrums ; to refrain from recommending them to 
their customers ; not to use any means of bringing them into public 
notice ; not to manufacture or to have manufactured any medicine, 
the composition of which is not made public; and to use every 
opportunity of exposing the evils attending their use, and the false 
means which are employed to induce their consumption." {Proc. 
Am. Pharm. Assoc., 1853, p. 17.) 



Am. Jour. Pharm. i j ne Patent Medicine Problem. 259 

June, 1914. J 

The agitation in the next decennium was largely centered about 
the manufacture of fluid extracts and the development of proprie- 
tary rights in preparations of this type, and ten years later we find 
a similar line of activity developing in connection with elixirs, which 
at that time were so popular. At the end of another decennium, 
however, the attention of members of the Association was again 
directed to patent medicines of the nostrum type by a resolution 
offered by Prof. A. B. Prescott, of Ann Arbor, to the effect that a 
committee of three members be appointed to agree upon the most 
feasible and suitable legislation to secure a sufficient statement of 
the composition of proprietary medicines, on the package of the 
same, and the more feasible and efficient action to be taken by the 
Association in regard to the matter. The committee appointed con- 
sisted of Albert B. Prescott, Frederick Hoffmann and Charles Rice. 
This committee, at the succeeding meeting of the Association, pre- 
sented a lengthy report on the nature of desirable legislation regard- 
ing the manufacture and sale of proprietary remedies, and also a 
draft of an act regulating the sale of proprietary medicines. The 
committee in its report offered a resolution which was subsequently 
adopted by the members of the Association present, to the effect 
" that it is the deliberate opinion of this Association that the labels 
of proprietary medicines ought to' carry a statement of their con- 
stituents." {Proc. Am. Pharm. Assoc., 1885, v. 33, pp. 394-398.) 
As evidence of the need for action along these lines the committee 
said in part: 

" All medicines, and articles used as such, concern the health of 
those who use them and put dependence upon them. By action or 
failure of action, a medicine is liable to prove hurtful when mis- 
applied. Therefore, it is the right of a purchaser of a medicine to 
receive information of its constituents, their names and propor- 
tional quantities. And it is a legitimate act of the State — so far as 
it deems expedient — to see to it that such information, in printed 
form, is placed upon each package of articles of medicine, as a 
condition of their legal sale. 

" Moreover, legislation requiring the composition of medicines 
to be given to the consumer is entirely in accord with the spirit of 
the institutions of the United States, because it is legislation tending 
to secure him in the means of self-preservation. The purchaser of 
a medicine is provided with a record of its constituents, given in 
terms defined by published standards: now he may guide himself, 



260 



The Patent Medicine Problem. { Km jnlT\lu vtsx ' 



in his own discretion or with professional aid, by the information 
given in the record of constituents, or he may neglect to so guide 
himself, and depend upon advice given on the wrapper of the 
medicine, in the exercise of his personal responsibility. The State 
has done its duty, and given the individual the opportunity for the 
exercise of discretion. The opportunity has an educational value to 
the individual." 

The following year the Committee on Legislation, in its report of 
progress (Proc. Am. Pharm. Assoc., 1886, v. 34, p. 10, 154, 155), 
included a resolution to the effect that : 

" Whereas, All medicines concern the health of those who use 
them; and 

4k Whereas, The purchaser of a medicine selected by himself 
has the right to receive information of its constituents and their 
quantities; and 

" Whereas, The report and the draft of a law regulating the 
sale of proprietary medicines, which were accepted by the American 
Pharmaceutical Association at its meeting held in September, 1855, 
embrace a method whereby the above-mentioned objects may be 
secured; therefore, be it 

" Resolved, That the President and other officers of the Asso- 
ciation be authorized and instructed to present printed copies of the 
reports and of the action had in this Association upon said reports, 
to the Governors, to the Speakers of the Senates and Houses of 
Representatives, and to the State Boards of Health, of the different 
States of the United States ; also> to offer any services wherein these 
authorities may consider the cooperation of this Association desir- 
able or useful." 

This preamble and resolution was vigorously discussed and a 
motion that they be stricken from the minutes of the Association 
was defeated. The report of the Committee was then on motion 
accepted, and finally on motion of C. Lewis Diehl, seconded by C. 
S. N. Hallberg, the preamble and resolution were adopted. 

Despite the endorsement given the report of the Committee on 
Legislation, little or nothing of a practical nature appears to have 
been done. During the early years of the succeeding decade a few 
isolated papers on patent medicine abuses, from a public health point 
of view, were presented, but their readers found no following and the 
resolutions they offered appear to have been overlooked or ignored, 
while much of the time of the Association was devoted to the dis- 



Am Jour Pharm.) The Patent Medicine Problem. 261 

June, iyi4:. j 

cussion of a plan or plans to remedy the " cutting of prices." The 
seriousness with which time was wasted on the discussion of the 
several plans that were suggested at that time serves well to illus- 
trate the comparative importance that has been accorded the purely 
economic side of this problem by various branches of the drug trade. 

At the semi-centennial meeting of the American Pharmaceutical 
Association, in 1902, several papers were again presented, bearing 
on existing abuses in connection with patent and proprietary reme- 
dies. These papers dealt principally with the abuse of so-called 
proprietary medicines and their use by physicians, and perhaps con- 
tributed somewhat at least to the renewed interest on the part of the 
American Medical Association in matters relating to the use of 
secret or semi-secret remedies by medical practitioners. 

At the meeting of the American Medical Association in New 
Orleans in 1903, a number of papers were presented criticising 
medical journals for the nature and kind of advertising carried by 
them, and a resolution adopted by the then Section on Materia 
Medica and Pharmacy condemned much of the advertising then car- 
ried in the Journal of the Association itself. At this meeting of the 
Association provision was also made for pharmaceutical member- 
ship in the American Medical Association, and at the meeting in 
Atlantic City the following June a number of pharmacists were 
elected and the discussions on materia medica subjects, with the 
resolutions adopted at Atlantic City in 1904, no< doubt were directly 
responsible for the inauguration of a Council on Pharmacy and 
Chemistry, the object of which was to endeavor to differentiate 
between good and bad proprietary remedies used by or offered to 
physicians. 

A preliminary meeting of persons interested was held in Phila- 
delphia on December 29, 1904, and the Council itself was organized 
in Pittsburg on February 11, 1905. This Council was immediately 
set to work and by June of the same year the comprehensive and at 
that time startling report on the acetanilide mixtures was published 
in the Journal of the American Medical Association and, as was 
expected, precipitated the wrath, not alone of pharmaceutical manu- 
facturers, but also' of medical journals that depend so largely on 
their advertising pages for existence. The so-called acetanilide re- 
port served, however, to* arouse the better class of medical men to 
an appreciation of their duty as professional men and the endorse- 



262 The Patent Medicine Problem. { Am j^iqw!™' 

ment thus secured has contributed much to maintain the Council 
despite the attacks of moneyed interests within and without the 
membership of the Association. 

The work of the Council was later in the year efficiently aug- 
mented by the series of articles originally published in Collier's 
Weekly, by Samuel Hopkins Adams, on the " Great American 
Fraud," and subsequently reprinted in pamphlet form by the Amer- 
ican Medical Association. The Food and Drugs Act of June 30, 
1906, also contributed its share in support of the work of the Council. 
These several agencies have been further augmented by the stand 
taken by the Commissioner of Internal Revenue in regard to alcohol 
containing nostrums and by the assistance given by various state 
officials entrusted with the enforcement of local food and drug laws, 
so that at the present time there is considerable evidence to show 
that the efforts of the Council on Pharmacy and Chemistry have 
made a distinct impression on thinking laymen as well as on the 
more progressive members of the American Medical Association. 

Following the inauguration of the Council on Pharmacy and 
Chemistry, the American Medical Association organized a chemical 
laboratory in the Association building, and this laboratory, in addi- 
tion to the work on "proprietary remedies," has devoted consider- 
able time to the examination of so-called " patent medicines " or 
4t nostrums." The resulting analyses are usually published in the 
Journal and have been in part, at least, compiled in book form in a 
volume entitled " Nostrums and Quackery." 

This book has recently been reprinted in enlarged form, and its 
increasing circulation among well-informed laymen will contribute 
much to a better understanding of the patent medicine problem from 
a public health point of view, and should serve to prevent any pos- 
sible retrogressive action on the part of the American Pharmaceu- 
tical Association as an Association. 

In summing up this brief and admittedly incomplete survey of 
recent accomplishments to solve the " patent medicine " problem, it 
would appear that the questions involved are not to be considered 
as being answered until they are answered correctly, and that from 
the point of view of the public the influence of " patent medicines " 
on the health and welfare of the individual is the only factor deserv- 
ing of consideration. Bearing this latter fact in mind, it would 
appear desirable that all branches of the drug trade give the patent 



Am 'j^ne, r 'i9 P i4 arm '} Plea f or More Effective C 'ooperation. 263 

medicine problem renewed and serious consideration, and make an 
honest effort to adjust their interests in accord with the interests of 
the public and thus effectually counteract the frequently made asser- 
tion that the economic questions involved must outweigh all others 
so far as the drug trade may be concerned. 



A PLEA FOR MORE EFFECTIVE CO-OPERATION AMONG 
PHARMACEUTICAL ORGANIZATIONS. 

By W. B. Day. 

Even a superficial observer of pharmaceutical affairs must have 
been struck by the increase in the number of organizations which 
depend upon pharmacists for their membership. Not only have we 
the two great national associations but each commonwealth is more 
or less thoroughly organized with its state, county and city associa- 
tions. 

At first glance this situation appears most encouraging and seems 
to show an appreciation of the value of these organizations and a 
commendable spirit in affiliating with them and sharing their en- 
deavors and their advantages, but when we look into the matter 
more closely we find that with all these opportunities for affiliation 
with an active society, the majority of pharmacists remain indifferent. 

There are nearly fifty thousand drug stores in the United States 
and probably over seventy-five thousand qualified pharmacists. Less 
than five per cent, of these are members of the American Pharma- 
ceutical Association, and certainly not more than twenty per cent, 
are members of the National Association of Retail Druggists. Very 
few state associations include within their membership more than 
a fifth of the qualified pharmacists of their respective states. 

In some of the larger cities strong local associations exist, but, on 
the other hand, there are many counties and cities where organiza- 
tion has never been effected, or if effected has perished through dis- 
use and neglect. Contrast with this 'the situation in Great Britain, 
where, of all European countries, the conditions most resemble our 
own. The last report of the Registrar of the Pharmaceutical Society 
of Great Britain shows 7788 members out of 16,608 qualified phar- 
maceutical chemists and chemists and druggists. Allowing for those 
who have retired from business or are engaged in some other line 



264 Plea for More Effective Cooperation. | Am - j J u " e r - ^ rm 

of work, it is estimated that nearly two-thirds of the chemists and 
druggists of Great Britain are members of the national society. And 
the membership is growing steadily ; the increase has been twenty- 
five per cent, during the last ten years. 

The only reason for the existence of any organization is service to 
its members and to the profession which it represents. Are present 
conditions favorable to such service? Is there not a wasteful dupli- 
cation of effort? Should there not be a better correlation of or- 
ganized pharmaceutical activities? 

Pharmaceutical associations have done wonderfully well in leg- 
islation, in education, in the development of scientific pharmacy and 
in the spreading of a knowledge of both technical and business 
methods. Co-operation has solved many perplexing questions : 
dangers have been bravely faced, evils have been overcome, and yet 
a start has scarcely ] en made. 

The attention of pnarmacists has often been called to the chang- 
ing conditions which vitally affect our calling. Not only are these 
evidenced by the spread of commercialism, the development of chain 
stores and syndicates, the increased dispensing by physicians and the 
multiplication of hospitals and dispensaries, but, deeper than these — 
the drift of social legislation which in Great Britain has produced 
the National Insurance Act and in Germany has resulted in a state- 
controlled industrial insurance. We may as well face the possibility, 
if not the probability, of state-paid medical service, including state- 
furnished medicines in our own country, during the next generation. 
Judging from the lack of recognition accorded to pharmacists in 
our army, we are held in but low esteem by the federal government 
at the present time ; physicians, dentists and even veterinarians rank 
far above us in the largest arm of the government service. 

It is high time that all pharmaceutical organizations should care- 
fully consider a general affiliation and correlation such as shall 
assign to each its special field and avoid the present overlapping and 
duplication. More effective work will be possible only through such 
mutual relations, and will deserve and receive wider support by 
pharmacists. A united body of seventy-five thousand pharmacists 
would command respect and insure fair treatment in the coming re- 
adjustment and division of labor that is sure to come as a part of 
the social movement. 



University of Illinois School of Pharmacy. 



Am. Jour. Pharm. 
June, 1914. 



Efficiency in Drug Stores. 



265 



EFFICIENCY IN DRUG STORES. 
By C. C. Honsaker, P.D. 

This is the age of specialization. Lawyers, doctors, mechanics 
and ministers are specialists ; when needed they are consulted, they 
need and consult one another. We all recognize that no one man 
knows it all. Just as there are sick people that need competent 
counsel, so there are sick businesses that need attention from experts. 

The old time business expert was and is, in fact, somewhat like 
the old-time doctor. He administered tonics and palliatives instead 
of getting at the seat of trouble. 

By keeping records and making tests, chemists, pharmacists and 
physicians have been able to standardize certain medicines. 

It has been but recent, however, that the b .mess doctor was able 
to diagnose and apply a standardized remedy, or specific, to a sick 
business. 

This, however, has been accomplished by the two great efficiency 
engineers, Emerson, of New York, and Taylor, of Philadelphia. 
These men have gathered together the threads of activity, and woven 
them into the science known as efficiency. Efficiency means the 
ability to accomplish. Personal efficiency is the mental and physical 
ability to find, and take, the best, easiest, and quickest way to the 
desirable things of life. 

These principles are not new, you and I employ them every day, 
at least some of them. 

Just as Sheldon has analyzed the sale, so has Emerson analyzed 
the operations and procedures of hundreds of successful men, and 
found that thirteen (13) principles were involved, in part or whole, 
by them in their accomplishments. 

There are seven (7) practical principles, and six (6) ethical ones. 
To-day we will be concerned with the practical ones only. 

A sick business like a sick body always has one symptom that 
gives the most trouble, from which, tracing backward, the cause can 
be located by the trained expert You all know what this symptom 
of unscientific business is in the drug world. The rancorous sore in 
the side of the drug business is the long hours. This, however, is 
only a symptom or effect. The cause is much deeper. 

This thirteen (13) to fifteen (15) hour day is driving the best 



266 



Efficiency in Drug Stores. 



Am. Jour. Pharm 
June, 1914. 



men out of the business. The great cry of the retail druggist is, 
" that we cannot get competent men." 

The P. C. P. and other colleges give men good scientific training, 
which most of them never have an opportunity to use. The drug 
journals contain article after article about building up business; 
these are read, possibly, but seldom put into actual practice. The 
various organizations ask for action and attendance, but get little 
or none, although the advantages to be gained are obvious. Tradi- 
tion has established a routine in the drug store, which very few have 
been able to break away from, and those who do are usually con- 
demned. 

There is no hope for the man who works thirteen (13) to fifteen 
(15) hours a day. It's a losing game every way one looks at it. 

The philosophy of the business must be changed. It must be 
studied from the standpoint of the sale. 

Business is buying and selling. Selling is our objective point. 
Our drugs and merchandise must be organized toward making the 
sale. The sale is the point from whence the money comes. Sales 
and quick ones. The five (5) and ten (10) cent stores are based on 
the principle of small, quick sales. Your average sale in the drug 
store is from fifteen (15) to eighteen (18) cents. 

Efficiency, then, is the keynote. It is the only salvation. Mr. 
Emerson would probably try to pull the manager out of the mass of 
details first, so that he, the manager, could get a perspective of his 
business. So we will, on that assumption, try and apply the seven 
(7) principles to the manager first, since a business is but the length- 
ened shadow of a single individual. 

There is one thing that the druggist is fortunate in having, and 
that is twenty- four (24) hours a day. The trouble is that he does 
not use it advantageously. Twenty-four (24) hours, then, is a fixed 
quantity, fixed and unchangeable. Time is what we are trying to 
save, therefore we will use it as our basis. 

Standards. 

The first principles of scientific management is " Standards." A 
standard is a reasonable attainable maximum of desirability. Before 
standards can be established, however, many records must be made. 

A record is anything that gives information of any kind. Records 
play an important part in everything we do. Baseball furnishes an 
excellent example of the use of records. 

What we want, then, is a record of what the druggist does with 



Am. Jour. Pharm. 
June, 1914. 



Efficiency in Drug Stores. 



267 



his fourteen (14) hours each day. This is accomplished by the use 
of a special chart, conveniently divided into five (5) minute periods 
or squares. The efficiency engineer keeps an account of every five 
(5) minutes of the fourteen (14) hours, for a period of time, say 
for one (1) week. At the expiration of the allotted time the various 
minutes are classified, wasted time analyzed, and a standard estab- 
lished for each of the various operations. 

Possibly he filled fifty (50) prescriptions during the week and 
expended approximately thirteen (13) hours. The standard time, 
then, for filling one (1) prescription is fifteen (15) minutes under 
normal conditions. 

You will say that it is impossible to establish a standard for such 
a changeable and indefinite operation. That is what they all say. 
If it were easy it would have been done long ago. It can be done 
with a complex operation, having many factors, as well as with the 
simpler operations, such as shoveling, shaving or even writing your 
name. 

You now have an annotated topography of your duties. Your 
next move is to organize the operations into logical sequence. That 
brings us to the second principle. 

Planning. 

You now plan your operations. This you can do intelligently, 
since you are dealing with known facts. At this point of the reorgani- 
zation your business policy changes. You become the power behind 
the business. The customer, doctor, salesman and others cease to 
mould your business to suit them. You are becoming aggressive. 
You know how long it takes to make a sale. You make the sale 
and get away. The salesmen come and go when you say ; not when 
they want to. 

To plan, though, is not enough. The Pennsylvania Railroad 
might plan to run the twentieth century limited from New York to 
Chicago; but,. unless schedules were made, this plan would be use- 
less. One crew might run at breakneck speed and send the train to 
the junk pile; another so slow as to consume unnecessary fuel. So, 
in order to avoid those conditions, definite schedules are carefully 
made. Consequently, the next principle to be applied is schedules. 

Schedules. 

A plan is a general statement. 

A schedule is a definite itemized statement. 

So, now, each operation is looked after minutely, a definite time 



268 



Efficiency in Drug Stores. 



Am. Jour. Pharm. 
June, 1914. M 



for its beginning and completion established. Everything in the 
store is now beginning to organize itself toward carrying into effect 
this new element of activity. Everything must fall in line. You 
do not wait for anything. Your motive is based upon known facts, 
and you know that you are right. 

To be scientific there must be a way of showing results. There 
is, and it is calculated by the following method. 

Divide the actual number of hours employed by the standard 
number, and the result is your efficiency of supply, e.g., say the time 
wasted by various leaks to be three hours, and your standard is 
fourteen hours, the actual number of hours employed is the differ- 
ence between fourteen hours and three hours, or eleven hours. This 
eleven hours divided by the fourteen hours gives 78, your per cent, 
of efficiency of supply. 

However, a man may be 100 per cent, efficient in supply of time, 
and yet not be efficient in the use of time, e.g., a pharmacist spends 
thirty minutes in compounding one prescription. His standard ac- 
complishment for thirty minutes is two prescriptions. Actual 
accomplishment, which is one prescription, divided by standard 
accomplishment, which is two prescriptions, shows his usage of 
time to be 50 per cent. 

These same principles, remember, apply to equipment and 
material as well as time. You may be efficient in supply and not in 
use. You may be efficient in use and not in supply. You attain 
maximum efficiency only when you are efficient in both. This is 
calculated as end efficiency. End efficiency is computed by multi- 
plying your supply of time efficiency by your efficiency of use. 

The next principle is despatching. 

Planning, as you have seen, means looking ahead, deciding what 
is to be done, how much time is to be allotted the stunt, and what 
material and equipment are necessary to its accomplishment. 

Schedules assign to each stunt a definite time and place, and 
definite quantities and qualities of material. They also list the 
equipment necessary, both as to quantity and place, and the standard 
time for the operation of equipment. It is not enough to establish 
standards for time, material and equipment. It is not enough to 
plan ahead. It is not enough to write schedules, no matter how 
elaborate and perfect they may be. 

You must have action. In other words, the work or stunt must 
be despatched. Some of the well known examples of despatching 



Am. Jour. Pbarm. 

Juue, 1914. 



Efficiency in Drug Stores. 



269 



are the umpires at a professional baseball game, the directing " next " 
of a porter in the barber shop, and the train despatcher. 

The antithesis to despatching is procrastination. 

Procrastination is nearly always due to a tired body or brain ; 
again, the accusing finger points to the long hours. How can a man 
despatch an important operation or communication who is submerged 
by multifarious details? A train despatcher as well as an umpire 
must be up and above the thing he is directing. 

Connie Mack's method of directing from the bench is better 
than the old style of directing from the field. 

The principle of despatching is a simple one. It means that 
when the time comes to do a thing you should have everything on 
hand and prepared to do it, and do it. 

Standardising conditions. 

This is the fifth principle of efficiency. This is the principle 
which is universally misapplied and misconstrued to mean efficiency. 
Mention efficiency to the average druggist and he will tell you that 
he has the most efficient store in town. What he means is that he 
has systematized his store from a certain standpoint. Efficiency 
implies system, but system does not by any means imply efficiency. 
YoU can do a thing systematically wrong. 

From the moment the first principle is applied you began re- 
arranging and standardizing conditions. This is an indication of the 
interdependence of the thirteen principles. 

By learning each of the thirteen principles you apply the fifth 
principle consciously, and, therefore, more fully and effectively. 

There must be a place for everything, but that place can only be 
found after many trial conditions. At this point I wish to call your 
attention to the greatest loss in the drug business. The druggist 
finds himself doing many things which could be done by subordi- 
nates ; such as dusting, running errands, looking up phone numbers, 
selling stamps, dispensing soda water, etc. While learning the 
business he did not mind doing it, because he looked forward to the 
time when he would take on larger responsibilities. The time came 
with the responsibilities, but the menial labor remained just the same. 
How can a man, who fills the capacity of a menial, command respect? 
Justice to all includes justice to self. 

There are thousands of five and ten cent sales made in the drug 
store. You cannot afford to waste energy making them. They must 
sell themselves. They are what might be termed trailers, such as 



270 



Efficiency in Drug Stores. 



{ Am. Jour. Pharm 
\ June, 1914. 



corn cures, epsom salts, seidlitz powders, etc. You can only afford 
to spend energy on larger sales. 

This capacity to assign yourself, subordinates, material, etc., is 
calculated as efficiency of assignment. Consult your records, find 
the most profitable hour of employment. This is your standard 
worth for an hour. For example, suppose that for a given hour 
your efficiency of supply was 91.7 per cent.; in other words, that 
you profitably employed forty-five minutes out of the sixty in that 
hour. Your efficiency of use was 85 per cent. ; in other words, you 
folded, labelled and packed eighty-five seidlitz powders during that 
hour, where your standard number for that hour should have been 
one hundred. The end efficiency of supply and use, therefore, was 
eighty-hundredths of 91.7 per cent., or about 78 per cent. Since a 
girl might have folded, labelled and packed those eighty-five powders 
in forty-five minutes, and her wages for the forty-five minutes would 
have been twenty cents, the actual commercial value of what you 
accomplished during that hour was twenty cents. For the purpose 
of illustration, let us fix your standard worth at $1.00 for the hour. 
Twenty cents is 20 per cent, of $1.00; this is your efficiency of 
assignment for that hour. Your end efficiency for supply, use, and 
assignment is therefore 85 x 91.7 x 20 per cent., or 15.5 per cent. 

Efficiency of assignment is measured by the ratio between actual 
value of what is accomplished or produced in a given time or from 
a given material or a given equipment and the standard value of 
production for such time, material or equipment. 

All the work in learning and applying the first five practical prin- 
ciples of efficiency has been not only leading up to the sixth prin- 
ciple, but actually compelling you to apply it. 

The sixth principle is standardized operations. 

It is obvious that there is only one best, easiest and quickest way 
to do any given thing. 

There may be one hundred different ways of doing a thing. This 
brings the case under the mathematical law of probability. The 
chance that you may happen upon the one best, easiest and quickest 
way is only one in a hundred. To show how slight are the chances 
of happening to choose the right operation, Mr. Emerson cites the 
case of an executive whose work he was called upon to study. This 
man's working day was fifteen hours, and he was always " terribly 
busy." As he did not plan his work, but simply turned feverishly 
from one task to another as they presented themselves, he wasted 



Am. Jour. Pharm. 
June, 1914. 



Efficiency in Drug Stores. 



271 



twenty-five per cent, of his time. This reduced his efficiency of 
supply to 75 per cent. 

Because he worked too many hours a day to maintain a standard 
condition of health and mental vigor, he not only procrastinated, 
dragged his work and kept others waiting, but made many blunders. 
The correction of these, where correction was at all possible, con- 
sumed a great deal of time. Taking into consideration his slow 
accomplishment, subtracting the amount of time wasted in correct- 
ing blunders, and the amount of time consumed in doing things 
wrongly, which could not be corrected, his efficiency of use was 
greatly reduced. Since he was too busy and too harassed to plan 
his work, he did not standardize any of his conditions or operations, 
leaving these matters entirely to chance, with the result that his 
efficiency of use of time was only 60 per cent. Because he did not 
plan or study, it naturally resulted that he spent a great deal of his 
time doing unnecessary things, as, for example, keeping records, 
that were neither immediate, reliable, adequate nor permanent. He 
also wasted hours blundering along with trivial details that ought 
to have been unloaded upon a subordinate who would have done them 
far more efficiently. 

For these reasons- his efficiency of assignment was only 40 per 
cent., and his end efficiency (75 x 60 x 40) was 18 per cent. By 
means of the thirteen principles of efficiency he might have accom- 
plished just as much with far better quality in three hours as he 
had been accomplishing in fifteen hours. You know an analogous 
case. 

To get back to standardized operations. This is the phase of 
efficiency that you mostly read about in the magazines; it involves 
time and motion study. 

Without going into detail, I have tried to give you a perspective 
of the application of the principles of efficiency. This skeletonized 
elucidation leaves many questions unanswered that will naturally 
arise in your mind concerning their application to the drug busi- 
ness. You may not be able to see how they could possibly be appli- 
cable in the face of so many uncertainties, such as occur in the drug 
business. 

Like a Socialist I answer by saying that those uncertain obstacles 
would not exist under proper management. The drug business 
to-day is governed by outside influences. The task we have is to 
regain control and manage according to a definite business policy. 



272 



Progress in Pharmacy. 



f Am. Jour. Pharm. 
\ June, 1914. 



You do not know what to charge for a prescription, because you 
have not standardized the operation of compounding. It is difficult, 
that is why it has not been done, but it can be done. 

The seventh and last practical principle is written standard prac- 
tice instructions. School text books, periodicals and the pharma- 
copoeia are written standard practice instructions. 

It is a difficult thing to change one's style of doing anything; 
therefore, it is necessary to strike a form, and to do this definite 
instructions must be carefully followed until it can be done with 
little or no conscious effort. 

PROGRESS IN PHARMACY. 

A Quarterly Review of Some of the More Interesting Litera- 
ture Relating to Pharmacy and Materia Medica. 

By Martin I. Wilbert, Washington, D. C. 

Interest in matters relating to pharmacy appears to be about 
equally divided between progress in the revision of the Pharmaco- 
poeia of the United States and matters relating to legislation designed 
to further restrict the sale of opium, cocaine, and other potent or 
habit- forming drugs. 

Two additional instalments of abstracts of proposed changes 
with new standards and descriptions for the United States Pharma- 
copoeia, ninth revision, have been published and distributed. The 
first of these, a pamphlet of 59 pages, designated Part II, embraces 
most of the drugs of vegetable and animal origin and presents more 
comprehensive changes than any one of the other instalments of 
changes so far published. 

The Chemist and Druggist, London (1914, vol. 84, p. 565), in 
commenting on the proposed changes in the pharmacognosy of the 
U. S. P., voices the opinion that the general indications are that the 
monographs in the U. S. P. IX will be quite an advance upon those 
included in the present Pharmacopoeia. 

Part III of the abstract of proposed changes embraces most of 
the waters, solutions, spirits, extracts, fluidextracts, resins, tinctures, 
and miscellaneous galenicals. Pharmacists generally will be pleased 
to learn that all of the important changes proposed for the several 
official galenical preparations can be adequately reflected in somewhat 



Am. Jour. Pharm. 
June, 1914. 



Progress in Pharmacy. 



273 



less than 29 printed pages. This fact would appear to indicate that 
many of the official formulae have been found to be satisfactory and 
that the members of the. Executive Committee of Revision have 
exercised due care in the making of changes. 

Commenting on the recently published abstracts of laws regu- 
lating the production, sale, and Use of poisons and habit-forming 
drugs in this country, the Pharmaceutical Journal, London (1914, 
vol. 92, p. 278), says: 

The poison legislation of the United States consists of a multi- 
plicity of statutes of a not very effectual character, and a fundamental 
alteration of the law seems to be desired. During the year 1912- 
19 1 3, over forty State, territorial, or similar Legislatures were in 
session, and nearly if not quite all of these bodies enacted some form 
of .legislation designed directly or indirectly to affect the sale and 
use of poisons. But, notwithstanding this abundance of legislation, 
the poison laws of the United States are admittedly still far from 
perfect. 

" The Harrison anti-narcotic bill, so-called, is still pending in 
the Senate, with some probability that the original bill in a slightly 
amended form will become law during the present session of Con- 
gress. It is perhaps unfortunate that the subject of Federal anti- 
narcotic legislation has been unnecessarily complicated by the intro- 
duction of a number of amendments that can in no way assist in 
developing the primary object of the bill and will at best serve to 
complicate its enforcement should it become law." 

Boy land Bill. — The recently enacted New York State law, known 
as the Boylan Bill, prohibits the sale of habit-forming drugs except 
on the prescription of a licensed physician, but the provisions do not 
apply to the sale of domestic and proprietary medicines actually sold 
in good faith as medicines and not for the purpose of evading the 
law, " providing such remedies or preparations do not contain more 
than two grains of opium, or one-fourth grain of morphine, or one- 
fourth grain of heroin, or one grain of codeine, or ten grains of 
chloral or their salts in one fluidounce, or if a solid preparation in 
one avoirdupois ounce, nor to plasters, liniments, and ointments for 
external use only." If the prescription calls for more than four 
grains of morphine, thirty grains of opium, two grains of heroin, 
six grains of codeine, or four drachms of chloral, the authority for 
the prescription must be verified. — Pharm. Era, 19 14, vol. 47, pp. 
199, 200. 



274 



Progress in Pharmacy. 



Am. Jour. Pharm. 
June, 1914. 



International Opium Conference. (Editorial.) — Discusses a re- 
port on the correspondence respecting the second International 
Opium Conference. It appears that Greece has refused to sign 
without stating any reason, while Turkey has refused to take any 
part whatever in the Conference. Germany and Russia were also 
not ready to ratify the Convention, although they have signed. In 
spite of these facts it is claimed by the delegates that matters have 
advanced considerably and that a long step has been taken toward 
the attainment of unanimity. — C hem. and Drug., 1914, vol. 84, p. 458. 

Commenting on the above, Xrayser II (p. 491) says: " The 
Opium Convention, like Mahomet's coffin, is suspended between 
heaven and earth, and while in that state of suspense it is worthless 
as an instrument for any practical purpose. But while the Con- 
vention itself may fail as an administrative force, I hope its educa- 
tional value will not be lost sight of, and that we as chemists will 
do what we can, each in his own sphere, to limit the evils which the 
Convention in its essential features was intended to abolish. There 
always will be a legitimate demand for and use of cocaine and mor- 
phine, and there will also probably always be an illegitimate demand. 
If we conscientiously set ourselves to discourage the latter by a 
judicious method of satisfying the legitimate use of these drugs, 
then the evil, so far as we are concerned, will be as effectually 
scotched as it would be by the adoption of the most stringent legal 
enactments." 

Drug Addicts. — Brown, Lucius P., is quoted as saying: " The 
anti-narcotic law going into effect recently is serving to uncover a 
terrible state of affairs. Already we have issued 1360 permits in the 
State, a large proportion of these to Nashville people, allowing 
druggists to sell them narcotics for habit use. While one-quarter 
of a grain twice a day is sufficient for the non-user of morphine, it 
requires eight grains daily for the person with the habit. Those who 
are on our books as having permits use an average of 251 grains a 
month." — Pharm. Era, 1914, vol. 47, p. 233. See also /. Am. M. 
Assoc., 1914, vol. 62, p. 1427. 

Price Maintenance. (Editorial.) — Considerable interest is being 
manifested at the present time in H. R. 13305, a bill introduced by 
Representative Stephens, of New Hampshire, which is entitled : 
" A Bill to Prevent Discrimination in Prices and to Provide for 
Publicity in Prices to Dealers and to the Public." This bill has been 
endorsed by the American Fair Trade League and a number of re- 



Am j^neri9i4 rm '} Progress in Pharmacy. 275 

tail organizations, and seeks to legalize contracts between manu- 
facturers and dealers in articles of commerce produced under a trade 
mark or special brand. If enacted into law the bill would restore to 
manufacturers the rights supposedly existing under which the vari- 
ous contracts were developed in connection with the sale of so-called 
patent medicine. — Pharm. Era, 1914, vol. 47, pp. 145, 146. 

Annual Meetings. — The annual meetings of State and National 
Pharmaceutical Associations and of other related organizations are 
attracting cpnsiderable attention. This year the order of holding 
the two National Drug Association meetings will be reversed : the 
1 6th Annual Convention of Retail Druggists is to be held in Phila- 
delphia, August 17-21, and the 62nd Annual Convention of the 
American Pharmaceutical Association is to follow, in Detroit, August 
24-29, 1914. 

American Chemical Society. — The meeting of the American 
Chemical Society was held in Cincinnati, April 7-10. Fully 1500 
chemists attended and more than 150 papers were read before the 
various sections. 

Meeting of the American Medical Association. — The meeting of 
the American Medical Association this year is to be held in Atlantic 
City, July 22-26. The preliminary program published in the Jour- 
nal, May 16, 1914, contains an unusually interesting list of promised 
contributions. The Section on Pharmacology and Therapeutics 
will meet in the gymnasium of the Grammar School, on Ohio Ave- 
nue, and the program for this section, as usual, includes a number 
of papers of direct interest to pharmacists. The exhibition, both 
scientific as well as commercial, will be held in the Atlantic City 
Exhibition Building, corner of Kentucky Avenue and the Board- 
walk. The scientific exhibition particularly promises to be unusually 
interesting, in that an effort will be made to present the material in 
a collective form so as to be more readily studied. — /. Am. M. 
Assoc. ,.1914, vol. 62, pp. 1 592-1 609. 

The Pharmacist and Pure Drugs —A recent article in Public 
Health Reports (1914, vol. 29, pp. 1137-1144) calls attention to the 
reported results of analyses of a number of widely-used drugs and 
preparations, and points out that the proper enforcement of laws 
designed to regulate the practice of pharmacy, in conjunction with 
pure drugs laws, should relieve physicians and the public of any 
doubt as to the composition, purity, quality, and strength of all drugs 
and medicinal preparations used in the treatment of disease. Any- 



276 



Progress in Pharmacy. 



Am. Jour. Pharin. 
June, 1914. 



thing short of this is a reflection on pharmacy as a calling and should 
not be tolerated or allowed to continue. 

Laboratory Equipment of Pharmacists. (Floyd, Henry B.) — 
Some of the balances found in Washington drug stores were not sen- 
sitive to a grain, while others required a decided overweight before 
they would operate at all. Many of the weights used are inaccurate, * 
having been allowed to corrode or to collect dirt. Pharmacists are 
known to use avoirdupois and apothecary's ounces interchangeably 
without regard to their difference. Glassware, especially that of 
less experienced manufacturers, is frequently inaccurate. — /. Am. 
Pharm. Assoc., 1914, vol. 3, pp. 569-571. 

Weights and Measures. (Editorial.) — In enforcing the weights 
and measures statutes in various States the officials report some pecu- 
liar conditions in connection with the metrological equipment of drug 
stores. Of particular interest is the fact that many instances are 
reported of over-size measuring glasses and heavy weights. These 
can be accounted for in only one way : the druggist has been imposed 
upon by the dealer from whom the inaccurate weights and measures 
were obtained. It behooves pharmacists to see that their weights 
and measures are accurate, and that none but accurate weights and 
measures are used. No legal requirement should be necessary to 
assure the proper weighing and measuring of the components of a 
prescription. — /. N. A. R. D., 19 14, vol. 18, pp. 262, 263. 

Annual Reports of the Chemical Laboratory of the American 
Medical Association, Volume 6. — This little book of ninety-eight 
pages presents a report of the work done from January to December, 
191 3, and includes reprints of contributions, reports abstracted from 
the Journal, and reports not previously published. In addition to 
the work growing out of the investigations by the Council on Phar- 
macy and Chemistry, the laboratory's work includes the examination 
of " patent medicines," and the investigation of chemical questions 
connected with the Propaganda and the Queries and Minor Notes 
work of the Journal. 

" New and Nonofdcial Remedies/' — A book review of " New and 
Nonofficial Remedies " says that this book is a valuable work of 
reference which gives the gist of what is known about a great number 
of well-known remedies and medicinal agents. — Pharm. J., 1914, vol. 
92, p. 576. 

Useful Drugs. (Editorial.) — "A Handbook of Useful Drugs," 
issued by the Council on Pharmacy and Chemistry of the American 



Am. Jour. Pharro. 
June, 1914. 



Progress in Pharmacy. 



277 



Medical Association, is a selected list of important drugs suggested 
for the use of teachers of materia medica and therapeutics and to 
serve as a basis for the examination in therapeutics by State Medical 
Examining and Licensing Boards. The great aim of the compilation 
is to eliminate the mass of useless or superfluous drugs now in books 
on materia medica; it concerns products whose fixed value is gen- 
erally recognized, and, therefore, it is particularly fitted to serve 
as a text on which teachers of materia medica and therapeutics may 
base their instruction. *rhe properties, pharmacological action, ther- 
apeutic uses, and dosage of drugs are discussed concisely and in a 
practical manner. The methods of administration have received 
special attention, and there are occasional suggestions as to choice 
of a vehicle which will be of service to beginners in prescription 
writing. There is a table of solubilities of the medicaments in cold 
water and in cold alcohol, a pharmacological index, and a general 
index. The book may be studied profitably by the pharmacists and 
medical men of this country. — Pharm. J., 19 14, vol. 92, p. 278. 

Digest of Comments. — A book review of Hygienic Laboratory 
Bulletin No. 87, including the Digest of Comments on the Pharma- 
copoeia of the United States of America, and on the National For- 
mulary, for the Calendar year 191 1, says in part: " This volume is 
a rich source of references to articles in various journals and bulle- 
tins dealing in any way to the substances contained in the American 
Pharmacopoeia, and places the user in position to readily find the 
original references in which he may be interested. The book is a 
model of compilation, such as one would expect from an international 
pharmacopceial secretariat." — Pharm. Weekblad, 1914, vol. 51, pp. 
238, 239. 

The Era Formulary. — Compilations of recipes for various objects 
and purposes have long been of interest to the retail druggist, and few 
stores in which the ordinary miscellaneous drug business is done can 
be profitably conducted without one or more books of this type. 
The new Era Formulary just published presents a collection of nearly 
8000 formulas gathered from recognized authorities. The nine 
divisions of the volume include unofficial .pharmaceutical prepara- 
tions, toilet preparations, veterinary remedies, household remedies, 
paints, beverages, and miscellaneous preparations frequently called 
for by the customers of a live retail drug store. The material was 
compiled by William C. Alpers and Ezra J. Kennedy, and the book 
as published covers 521 large 8vo double-column pages, including an 



278 Progress in Pharmacy. { Am jime r 'i9u arm * 

index of 35 pages. As a compendium of suggestions for the up-to- 
date pharmacist this book should appeal to all pharmacists who are 
desirous of giving to their patrons the best possible service that they 
are capable of. 

Pharmaceutisch Weekblad. — The number of this journal for 
April 3, 19 14, concludes the fiftieth year of the publication and com- 
prises 155 pages devoted to historical reviews of the progress of 
pharmacy during the past fifty years. As a supplement the publishers 
present a pamphlet of 98 pages, entitled " Monumenta Pharmaceu- 
tical and containing a reprint of several historical papers of phar- 
maceutical interest. The first paper is a reprint of the communica- 
tion by M. de la Condamine, " Sur l'Arbre du Quinquina," published 
in Paris in 1740. The pamphlet also contains a reprint of the paper 
by F. W. Sertiirner (1817) in which he reports his discovery of 
morphine, a new base, and of meconic acid as being the principal 
constituents of opium. A paper by Smithson Tennant (1814) on 
the means of producing a double distillation by the same heat, a 
paper by John T. Barry (1819) on a new method of preparing phar- 
maceutical extracts, a paper by Thomas Thompson (1818) on Mr. 
Henry Tritton's patent for an improved apparatus for distillation, 
and a paper on the education of the apothecary, G. J. Mulder (1842), 
are also reprinted. This supplement is exceptionally interesting, in 
that it makes available for ready reference a number of the more 
important contributions to pharmaceutical literature. 

Acetyline is a new name used in some portions of Europe for 
acetylsalicylic acid, and serves to further complicate the nomenclature 
of this now widely used substance. — Pharm. Weekblad, 1914, vol. 
51, p. 578. ^ 

Afridol is described as sodium mercuri-o-toluylate, said to be an 
efficient substitute for corrosive mercuric chloride. Afridol is said 
to be active in dilutions up to 1 : 100,000, while corrosive sublimate 
is no longer active in solution of 1 : 50,000. — Sudd. Apoth.-Ztg., 
1914, vol. 54, p. 62. 

Alypin. — Lichtenstein, L., refers to the sudden fatal collapse 
after injection of alypin in a case reported by Proskauer and one by 
Ritter. Schroder and Garash have also reported cases of con- 
vulsions, stupor, and asphyxia after its use, and Lichtenstein adds 
another to this group. — /. Am. M. Assoc., 1914, vol. 62, p. 975. 

Amorphous Phosphorus. (Anon.) — A criticism on the introduc- 
tion of amorphous phosphorus, a practically inert substance which is 



Am. Jour. Pharm. 
June, 1914. 



Progress in Pharmacy. 



279 



being offered as a " valuable therapeutic agent." — /. Am. M. Assoc., 
1914, vol 62, pp. 793, 794. See also pp. 1033-1035. 

Argyrism. — Crispin, Antonio M., reports a case of argyrism fol- 
lowing the use of collargol. The administration of potassium iodide 
had not the slightest effect on the resulting color of the skin. The 
subsequent administration of hexamethylenamine caused the color to 
fade and become several shades lighter. — /. Am. M. Assoc.] 1914, 
vol. 62, p. 1394. 

As pido spermine. (Cow, Douglas.) — Experimental observations 
on the action of the alkaloids of quebracho. Quebrachine is by far 
the most toxic of the four alkaloids investigated. In small doses 
quebrachine exerts a stimulating action on the central nervous sys- 
tem, as also do the other alkaloids. The only obvious objective effect 
of this is seen in the respiration, which becomes both quicker and 
deeper. — /. Pharmacol, and Exper. Therap., 1913-1914, vol. 5, pp. 
341-356. ^ 

Aspirin. (Reed, Edward N.) — Report of a case of idiosyncrasy 
to aspirin (acetylsalicylic acid) in which vomiting, cyanosis, and 
oedema followed the ingestion of 5 grains of the drug. No treatment 
was instituted, and in about six hours the patient was comfortable. — 
/. Am. M. Assoc., 1914, vol. 62, p. 773. See also p. 797. 

Creolin consists of the glycerides of fatty acids along with chol- 
esterins, lecithin, and ethereal oil, all of which are found in yeast. 
It is prepared by extracting fresh purified beer yeast with alcohol 
and separating the dissolved fat from the alcoholic extract by suit- 
able means. Creolin is said to be useful in furunculosis, acne, sycosis, 
and similar affections of the skin. It is also said to be useful in 
habitual constipation, leucorrhoea, erosions of the vagina and cervix, 
and similar diseases. — -/. Am. M. Assoc., 1914, vol. 62, p. 931. 

Cocaine. (Editorial.) — The demand for cocaine for legitimate 
medicinal uses appears to have diminished considerably in recent 
years. Some of the large firms, which formerly handled many thou- 
sands of ounces of cocaine in the course of the year, now do not sell 
so many hundreds, while other firms which also dealt in the article 
in not inconsiderable quantities now sell practically none. — Pharm. 
J., 1914, vol. 92, p. 466. 

Collargol. (Eisendrath, Daniel E.) — A preliminary note on the 
effect of injecting collargol into the renal pelvis. The report states 
that death resulted in animals from extensive and widely-distributed 
collargol embolism, and the author believes that these experiments 



28o 



Progress in Pharmacy. 



Am. Jour. Pharm. 
June, 1914. 



offer for the first time a logical explanation of deaths observed in the 
human being. — /. Am. M. Assoc., igi4, vol. 62, pp. 1392, 1393. 

Crotalin. — Anderson, John F., reports a fatal case of bacterial 
infection from the use of the venom of Crotalus horridus dissolved 
in water. He also reports the examination of 95 ampoules of cro- 
talin solution prepared by four different firms, 35 of which (38.8 
per cent.) were found not to be sterile. — /. Am. M. Assoc., 1914, 
vol. 62, pp. 893-895. 

Crotalin. (Yawger, N. S.) — Report on six cases of epilepsy 
treated with crotalin. Two patients were uninfluenced; two were 
worse during the treatment ; one early in the course developed such 
intolerant toxic symptoms that further experimentation was unjus- 
tified, and the last patient died two and a half months after treatment. 
— /. Am. M. Assoc., 1914, vol. 62, pp. 1533-1535. 

Cymarin. — A glucoside obtained from Canadian hemp, said to 
have an action on the circulation somewhat similar to digitalis and 
to be an efficient diuretic. — Sudd. Apoth.-Ztg., 1914, vol. 54, p. 62. 

Diachylon. (Editorial.) — Newcastle-on-Tyne pharmacists have 
done one of the best things that we have heard of recently, by re- 
solving to stop the sale of diachylon plaster in the lump, or any other 
form which may be taken internally. They have come to this reso- 
lution after hearing from Mr. T. Maltby Clague particulars of the 
cases of lead poisoning among women due to diachylon. Mr. Clague 
has had excellent opportunities in his investigations with Sir Thomas 
Oliver, M.D., of seeing the damage that is done by diachylon, and 
he considers that all self-respecting registered chemists should refuse 
to sell the stuff to anyone. Its legitimiate use as a plaster is so trifling 
nowadays that the public would suffer little inconvenience if they 
could not buy it from pharmacies conducted under the act of 1908. — 
Chem. and Drug., 1914, vol. 84, p. 458. 

Erepton is a product prepared by the digestion of meat and con- 
sisting largely of amino-acids thus produced. It is prepared by the 
successive action of pepsin-hydrochloric acid, trypsin and erepsin 
on meat freed from fat and tendon ; the end-product is then desic- 
cated. Erepton is a brownish, hygroscopic powder, easily soluble 
in water and having an odor and taste suggestive of meat extract. — 
/. Am. M. Assoc., 1914, vol. 62, p. 1559. 

Eusitin. — Tablets containing the mucin substances obtained from 
Althcea rosea syriens. Intended for use in the treatment of obesity, 
the employment of those tablets being based upon their property of 



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June, 1914. 



Progress in Pharmacy. 



281 



abolishing the feeling of hunger from which patients suffer who are 
placed on a limited diet. — Chem. and Drug., 1914, vol. 84, p. 443. 

Friedmann Remedy. (Editorial.) — Several recent German 
articles on the Friedmann remedy appear to be uniformly unfavor- 
able. They add to the testimony already given in this country that the 
Friedmann remedy is not inefficient alone, but also may be dangerous. 
All reliable reports regarding the treatment of patients by Fried- 
mann's method seem to show either that it is actually injurious or 
else that it is less efficient than other well-known and less dangerous 
means of treatment. — /. Am. M. Assoc., 1914, vol. 62, p. 1407. See 
also pp. 1206 and 1343. 

Hydrogen Peroxide. (Stewart, R.) — There is really a very curi- 
ous amount of ignorance prevalent as to hydrogen peroxide. The 
ordinary hydrogen peroxide of commerce is now an article sold by 
the ton, and even for many purposes of the drug trade this quality 
answers admirably. The ordinary commercial commodity, however, 
does not compare in stability with the higher-priced product used 
for medicinal purposes. The whole question is one of price. So 
long as drug stores, hospital authorities, and others expect a product 
at the very lowest possible price, it is hardly fair to expect manu- 
facturers to deliver goods which it would cost two or three times the 
selling price to produce. — Pharm. J., 1914, vol. 92, p. 353. 

The Hypophosphite Fallacy. (Anon.) — A false therapeutic no- 
tion born of speculation soon dies a natural death if exposed unsup- 
ported to the cold world of facts, but when nursed by commercial 
interests it may be kept alive for generations. Interesting examples 
of this, to name but two or three, are the misconceptions perpetuated 
during the past half century concerning " lithia," the " natural " 
salicylates, and the hypophosphites. In spite of reliably reported 
observations, the hypophosphites continue to be employed by many 
practitioners, largely because the theory on which their use is based 
was thought to be plausible at the time when chemical theories were 
popular and gained a certain recognition and were adopted without 
scientific investigation. These theories were subsequently taken up' 
by certain manufacturers and became a commercial asset, so that, 
as a result, a theory which uncommercialized would have died of 
inanition, was kept alive by continued advertisement. — /. Am. M. 
Assoc., 1914, vol. 62, pp. 1346, 1347. 

Ipecacuanha. (Van der Wielen and Reens.)— An assay of the 
same sample of ipecacuanha by the methods official in the Pharmaco- 



282 



Progress in Pharmacy. 



Am. Jour. Pharm. 
June, 1914. 



poeias named gave the following wide variation in results : Japanese 
Pharmacopoeia, 1.78 per cent. ; Belgian, 1.71 per cent. : United States, 
1.67 per cent.; Swiss, 1.735 P er cent.; Swedish, 1.735 P er cent.; 
Austrian, 2.15 per cent.; Hungarian, 2.13 per cent.; Dutch, 2.06 per 
cent; German, 1.54 per cent.; Italian, 2.03 per cent. These results 
point to the desirability of an international process and standard. — 
Pharm. J., 1914, vol. 92, p. 541. 

Leukozon. — Calcium perborate mixed with talc and standardized 
to a content of 5 per cent, of available oxygen. Used as an antiseptic 
dusting powder. — Chem. and Drug., 1914, vol. 84, p. 443. 

Liquid Paraffin. — Peck, J. Wicliffe, in discussing the production 
and use of liquid paraffin^ says : " It has been stated that liquid paraffin 
should not be given with meals or during the process of digestion, 
as it prevents the pancreatic emulsiflcation of fats. The experiments 
in vitro I do not think would be repeated in the body. From prac- 
tical experience, just after a meal is the time I should suggest. If 
taken on an empty stomach the oil passes through very often un- 
mixed with the stools and taking the usual thirty hours. When 
given in excess to animals it passes through with apparently no 
colorable fats dissolved." — Pharm. J., 19 14, vol. 92, p. 509. 

Novotryposafrol. — A derivative of tryposafrol, for use in try- 
panosome infections and also in veterinary medicine. — Chem. and 
Drug., 1914, vol. 84, p. 443. 

Perydal. — An antiseptic dusting powder, containing formalde- 
hyde and Peruvian balsam. It is used as a general antiseptic for 
wounds, for dusting in the stockings, and for infants. — Pharm. J., 
1914, vol. 92, p. 286. 

Phenolphthalein. (Editorial.) — A recent report of the labora- 
tories of bacteriology and physiologic chemistry at the Jefferson 
Medical College in Philadelphia states that in twenty experiments, 
in each of which, before beginning the trials, the subject's urine 
showed no trace of albumin by delicate tests, 24-hour-specimen, col- 
lected after the administration of phenolphthalein in a from i-grain 
to 2-grain dose, gave positive tests for protein in every case. *The 
amount of albumin varied from a trace up to 0.25 per cent, by 
Esbach's quantitative method. The precipitate in many of the cases 
was tested and found to be insoluble in alcohol. Traces of phenol- 
phthalein were demonstrated in the urine. The albuminuria lasted 
from one to three days. — /. Am. M. Assoc., 1914, vol. 62, p. 1560. 

Phenolphthalein-agar is agar-agar impregnated with phenolph- 
thalein, 100 Gm. containing 3 Gm. of phenolphthalein. Phenolphtha- 



Am. Jour. Pharm. 
June, 1914. 



Progress in Pharmacy. 



283 



lein-agar is prepared by impregnating 1000 Gm. of agar-agar with a 
solution obtained by dissolving 30 Gm. of phenolphthalein in a mix- 
ture of 2000 Cc. of water and 700 Cc. of alcohol and drying the 
impregnated agar-agar slowly. — /. Am. M. Assoc., 1914, vol. 62, 
p. 1 168. 

Quinine Poisoning. (Underhill, Elizabeth C.) — Report of a case 
of quinine poisoning in a woman, age 20, who took at one dose 100 
2-grain quinine pills. The toxic symptoms were accompanied by 
impairment of vision, which improved gradually. — /. Am. M. Assoc., 
1914, vol. 62, pp. 1396, 1397. See also p. 920. 

Quinine-urea Hydrochloride. (Abstract.) — There is a certain 
element of danger attending the use of quinine-urea hydrochloride as 
a local anaesthetic. It has been pointed out that sloughing may follow 
its use when a solution stronger than 3 per cent, is used. An exten- 
sive abscess has followed the use of a 1 per cent, solution for the 
removal of internal hemorrhoids, and two cases of sloughing follow- 
ing the use of a 2 per cent, solution in similar operations are re- 
corded. The general opinion is that solutions of this substance should 
not be stronger than 1 per cent. ; some observers recommend even 
weaker solutions, and with proper attention to technic bad effects 
may be greatly reduced. — Pharm. J., 1914, vol. 92, p. 368. 

Riopan. — A concentrated preparation of ipecacuanha sent out 
as a brownish powder, soluble in water. It is standardized to con- 
tain 50 per cent, of ipecacuanha alkaloids in the form of their hydro- 
chlorides; the other more or less inert substances are also present. 
One part of riopan is equivalent to 20 parts of ipecacuanha root. — 
Chem. and Drug., 1914, vol. 84, p. 443. 

Salvarsan. — No one can dispute the statement that many of the 
deaths from salvarsan have been caused by its ill-considered use, 
either in the face of contra-indications or in too large or too fre- 
quent dosage, but to argue from this that the fatalities are therefore 
not due to salvarsan and that salvarsan is not toxic is far from 
logical. The unwise use of salvarsan may be expected as a result of 
such arguments, and the stubborn denial of the toxicity of the drug 
has encouraged its careless administration. — /. Am. M. Assoc., 1914, 
vol. 62, p. 1 176. 

Neosalvarsan. (Anon.) — Seven deaths have occurred in the Los 
Angeles Hospital within two days following intraspinal injections 
of a solution of neosalvarsan in autogenous serum, and another 
patient is reported as being likely to die. — /. Am. M. Assoc., 1914, 
vol. 62, pp. 861, 862. See also pp. 957, 958. 



284 



Progress in Pharmacy. 



Am. Jour. Pharm. 
June, 1914. 



Sarsaparilla. (Editorial.) — The proposition to include in the 
Pharmacopoeia of the United States, Mexican, Honduras, Para, and 
Jamaica varieties of sarsaparilla is especially interesting in connec- 
tion with the revision of the British Pharmocopceia, it being under- 
stood that this good old-fashioned drug does not commend itself 
to the Oxford Street savants, who desire to relegate it to the limbo 
of ex-official things. — Chem. and Drug., 1914, vol. 84, p. 566. 

Serum Treatment of Tetanus. (Editorial.) — The great value of 
antitetanus serum as a preventive is unquestioned. As a specific 
cure, however, this serum has fallen far short of the earliest expec- 
tations ; it even has been asserted that so far the statistics and the 
evidence obtained from watching patients treated with serum do not 
indicate that it has any real curative value. It has been shown ex- 
perimentally, however, that antitetanus serum may save animals 
already suffering from the symptoms of an otherwise fatal intoxi- 
cation, but in order to accomplish this result the serum must be given 
in several hundred times the quantity required merely to protect, and 
it must be injected within a short time, from 24 to 36 hours, after 
the onset of the tetanus. Furthermore, it cannot be denied that the 
weight of statistics favors the serum. — /. Am. M. Assoc., 1914, vol. 
62, pp. 1 174, 1 175. 

Silver Methylene Blue contains 24 per cent, of silver. Is being 
tried as an antiseptic, as it is assumed to possess a powerful bacteri- 
cidal action in various infectious processes. — Chem. and Drug., 1914, 
vol. 84, p. 443. 

Tenosin. — The active constituents of ergot are now contracted 
to three substances, ^-oxyphenolethylamine, beta-imidazolylethylam- 
ine, and ergotoxin. For therapeutic purposes only the first two 
substances come into consideration, as the ergotoxin is the gengren- 
producing substance of ergot. Tenosin is said to be a mixture of the 
two amines mentioned above, and is available either in the form of 
ampoules or as a liquid for internal administration. — Sildd. Apoth- 
Ztg., 1914, vol. 54, p. 63. 

Theobromine Sodium, Salicylate. (Puckner and Leach.) — Report 
of an investigation of the available brands of theobromine sodium 
salicylate. The results of the investigation, which are in the form of 
a table, show some variation in the moisture content and also in the 
actual theobromine content of the dried specimens; the variation is 
unimportant. .The products in their original state (undried), as 
compared in relation to the theobromine content (the highest per- 



Am. Jour. Pharm. 
June, 1914. 



Amendment to Regulation p. 



285 



centage of theobromine being 48.61, the lowest 45.24), reveal a 
variation of only about 3 per cent., a variation which is negligible in 
the case of such drugs as theobromine. — /. Am. M. Assoc., 1914, 
vol. 62, pp. 1 108, 1 109. 

Tobacco Snuff. (Anon.) — The Supreme Court of North Dakota 
holds constitutional the antisnuff act of that State of 1913, which 
makes it unlawful to import, manufacture, distribute, or give away 
snuff, or substitute therefor, under whatever name called. — /. Am. 
M. Assoc., 1914, vol. 62, p. 1424. 

Tricarbin. — Under this name, or as glycarbin, glyceryl carbonate 
has been introduced as a chemical inert diluent and basis for medici- 
nal substances and galenical preparations such as pills, powders, 
tablets, and cosmetic preparations. It occurs as a crystalline non- 
hygroscopic, permanent, insoluble powder ; it melts with decomposi- 
tion at about 149 C. — Pharm. J., 1914, vol. 92, p. 286. 

Vitamines. (Anon.) — Vitamine is the name given to a substance 
which is believed to be necessary to prevent the nervous lesions 
characteristic of beriberi. It is regarded as an antineuritic agent 
naturally present in rice, the removal of which by polishing causes 
the symptoms of the disease to appear. The name appears to be de- 
rived from vita (life and amine), indicating its chemical character. 
The substance was at first thought to be a pyrimidine base with the 
following formula : C 17 H 20 O 7 N 2 . It was at first believed to have the 
constitution of a ureide, but in his latest work Funk states that the 
nitrogen is not present in the amino form. Vitamine was first found 
in rice and was connected with beriberi. Other substances of similar 
character were subsequently discovered, and the name has become 
descriptive of a class. Vitamine was discovered in 191 2 by Casimir 
Funk. — /. Am. M. Assoc., 19 14, vol. 62, p. 1349. 



CORRESPONDENCE. 

Amendment to Regulation 9, Relating to Guaranties by Wholesalers, 
Jobbers, Manufacturers, and Other Parties Residing in the 
United States to Protect Dealers from Prosecution. 

Regulation 9 of the Rules and Regulations for the enforcement of 
the Food and Drugs Act, June 30, 1906 (34 Stat., 768), United 
States Department of Agriculture, is hereby amended, effective May 
1, 1915, so as to read as follows: 



286 



Amendment to Regulation p. 



f Am. Jour. Pharm. 
\ June, 1914. 



REGULATION 9. GUARANTY. 

(Section 9.) 

(a) It having been determined that the legends " Guaranteed 
under the Food and Drugs Act, June 30, 1906," and " Guaranteed 
by (name of guarantor), under the Food and Drugs Act, June 30, 
1906," borne on the labels or packages of food and drugs, accom- 
panied by serial numbers given by the Secretary of Agriculture, are 
each misleading and deceptive, in that the public is induced by such 
legends and serial numbers to believe that the articles to which they 
relate have been examined and approved by the Government and 
that the Government guarantees that they comply with the law, the 
use of either legend, or any similar legend, on labels or packages 
should be discontinued. Inasmuch as the acceptance by the Sec- 
retary of Agriculture for filing of the guaranties of manufacturers 
and dealers and the giving by him of serial numbers thereto con- 
tribute to the deceptive character of legends on labels and packages, 
no guaranty in any form shall hereafter be filed with and no serial 
number shall hereafter be given to any guaranty by the Secretary 
of Agriculture. All guaranties now on file with the Secretary of 
Agriculture shall be stricken from the files, and the serial numbers 
assigned to such guaranties shall be canceled. 

( b) The use on the label or package of any food or drug of any 
serial number required to be canceled by paragraph (a) of this 
regulation is prohibited. 

(c) Any wholesaler, manufacturer, jobber, or other party resid- 
ing in the United States may furnish to any dealer to whom he sells 
any article of food or drug a guaranty that such article is not adul- 
terated or misbranded within the meaning of the Food and Drugs 
Act, June 30, 1906, as amended. 

(d) Each guaranty to afford protection shall be signed by, and 
shall contain the name and address of, the wholesaler, manufacturer, 
jobber, dealer, or other party residing in the United States making 
the sale of the article or articles covered by it to the dealer, and shall 
be to the effect that such article or articles are not adulterated or 
misbranded within the meaning of the Federal Food and Drugs Act. 

(e) Each guaranty in respect to any article or articles should be 
incorporated in or attached to the bill of sale, invoice, bill of lading, 
or other schedule, giving the names and quantities of the article or 
articles sold, and should not appear on the labels or packages. 



Am. Jour. Pharm. ) 
June, 1914. / 



Abolition of Legend Postponed. 



287 



(/) No dealer in food or drug products will be liable to prosecu- 
tion if he can establish that the articles were sold under a guaranty 
given in compliance with this regulation. 

W. G. McAdoo, 

Secretary of the Treasury. 
D. F. Houston, 

Secretary of Agriculture. 
William C. Redfield, 
Secretary of Commerce. 

Washington, D. C, May, 5, 1914. 



ABOLITION OF GUARANTY LEGEND POSTPONED. 

Revised Food Inspection Decision Allows Manufacturers Additional 
Year in Which to Exhaust Stock of Labels. 

Washington, D. C, May 29, 19 14. It was announced to-day that 
it had been decided to postpone the effective date of Food Inspection 
Decision 153, which, in substance, abolishes, after May 1, 19 15, the 
present guaranty legend on food and drugs. 

This legend, now in general use by manufacturers, is " Guar- 
anteed by (name of guarantor) under the Food and Drugs Act." 
The Secretaries of the Treasury, Agriculture, and Commerce have 
found it to be misleading and deceptive. Many people have been 
induced to believe that all articles labelled with the legend have been 
examined and approved by the Government. The facts are that 
putting the legend on labels by manufacturers is entirely voluntary, 
and that the Government never guarantees the wholesomeness or 
purity of food or drug products. 

It appears that, acting in accordance with the regulation now in 
force, which permits the legend, many manufacturers have supplied 
themselves with large stocks of labels which cannot be used up by 
May 1, 191 5. The result is that if the regulation, as amended by 
Food Inspection Decision 153, should go into effect May 1, 191 5, 
large losses would accrue to citizens who have expended their money 
for labels in good faith and in an effort to comply with existing 
regulations. 

To meet this situation the effective date of the amendment to the 
regulation will be postponed until May 1, 1916, and as to products 
packed and labelled prior to May 1, 191 6, in compliance with law and 
with the present regulations, it will be postponed until November r, 



288 Constituents of Senna. { 



Am. Jour. Pharm. 
June. 1914. 



1 916. Meanwhile, manufacturers may, and doubtless many will, 
label their good in compliance with the new regulations. 
The decision is as follows: 

FOOD INSPECTION DECISION NO. 1 55. 

Changing Effective Date of Food Inspection Decision No. 15J, 
which Amends Regulation 9, Relating to Guaranties by Whole- 
salers, Jobbers, Manufacturers, and other Parties Residing in 
the United States to Protect Dealers from Prosecution. 
The effective date of Food Inspection Decision No. 153, issued 
May 5, 1914, is hereby postponed until May 1, 1916; Provided, That 
as to products packed and labelled prior to May 1, 1916, in accordance 
with law and with the regulations in force prior to May 5, 19 14, it 
shall become effective November 1, 1916; And Provided Further, 
That compliance with the terms of Regulation 9 of the Rules and 
Regulations for the Enforcement of the Food and Drugs Act as 
amended by Food Inspection Decision No. 153 will be permitted at 
any time after the date of this decision. 

C. S. Hamlin, 
Acting Secretary of the Treasury. 

D. F. Houston, 
Secretary of Agriculture. 

Wm. C. Redfield, 
Secretary of Commerce. 

Washington, D. C, May 29, 1914. 



CURRENT LITERATURE. 

Constituents of Senna. 

An investigation of senna leaves to determine the exact constit- 
uents present revealed many interesting things about this well-known 
drug. 

Tinnevelly senna leaves (Cassia angustifolia, Vahl) ; senna leaves 
from Lima, Peru, which were found to be botanically identical with 
the Tinnevelly leaves, and Alexandrian senna leaves were used. 

An alcoholic extract of the Tinnevelly leaves, when distilled with 
steam, yielded a small amount of an essential oil. From the portion 
of the extract which was soluble in water the following substances 
were isolated : Salicylic acid, rhein, C 15 H 8 O e ; kaempferol, C 15 H 10 O 6 ; 
aloe-emodin, C 15 H 10 O 5 ; kaempferin, C 27 H 30 O 16 , 6 H 2 (m. p. 185 - 
195 ), a new glucoside of kaempferol; a mixture of the glucosides 



Am 'j^ne r 'i£4 arm *} Constituents of Senna, 289 

of rhein and aloe-emodin ; the magnesium salt of an unidentified 
organic acid. The aqueous liquid furthermore contained a quantity 
of a sugar which yielded d-phenylglucosazone (m. p. 216 ), and some 
brown, amorphous products, which, on treatment with alkali, gave 
kaempferol, together with small amounts of rhein and aloe-emodin. 
Some amorphous, glucoside material was also present. 

The portion of the alcoholic extract which was insoluble in water 
consisted of a soft, dark green resin, which amounted to 7.0 per 
cent, of the weight of the leaves employed. From this material, 
which contained considerable chlorophyll and amorphous products, 
there were isolated, in addition to some of the substances mentioned 
above, the following compounds : Myricyl alcohol ; a phytosterol, 
C 27 H 4e O ; a phytosterolin, C 33 H 56 6 ; palmitic and stearic acids. 

The senna leaves from Lima, Peru, were found to contain all 
the above-mentioned compounds, with the exception of the magne- 
sium salt, and, in addition, worhamnetin. A glucoside of worhamne- 
tin was also present in association with glucosides of kaempferol, 
rhein, and aloe-emodin, but no pure compound could be isolated from 
the mixture. 

Alexandrian senna leaves yielded, in addition to myricyl alcohol 
and a phytosterolin, rhein, aloe-emodin, kaempferol, and worhamne- 
tin. These four substances were also present in the form of gluco- 
sides, and in much greater proportion as such than in the free state. 

The statements of Tschirch and Hiepe (Arch. Pharm., 1900, 
238, 427) that senna leaves contain " sennawoemodin," " senna- 
chrysophanic acid" (chrysophanol), and a "substance, C 14 H 10 O 5 ," 
could not be confirmed, it having been ascertained that the anthra- 
quinone derivatives present consist solely of rhein and aloe-emodin. 
In this connection it may be noted that a mixture of approximately 
equal quantities of the last-mentioned two compounds has the em- 
pirical composition and properties assigned by Tschirch and Hiepe 
to the " substance C 14 H 10 O 5 ." Furthermore, the " sennarhamne- 
tin " of the last-mentioned authors has been found to be identical 
with the uorhamnetin previously described by Perkin (T., 1896, 69, 

1658). 

Frank Tutin, from the Transactions of the Chemical Society, 
vol. 103, 1913. London. J. K. T. 

The Serum Treatment of Hay Fever. — In a pamphlet, by 
Lewis M. Somers, M.D., published by Fritzsche Brothers, New 
York, a summary of ten years' experience in the use of pollen 



290 



The U. S. Pharmacopoeia. 



Am. Jour. Pharm. 
June, 1914. 



antitoxines, Dr. Somers demonstrates that from the very nature 
of the disease no single therapeutic agent can act as a specific, nor 
even modify the symptoms in every case. The serum formerly used 
was prepared by the action of the pollen toxin of either spring or 
fall plants upon the horse, and the resulting serum bodies being 
the therapeutic agent employed. Many experiments with the pollen 
toxin upon individuals subject to hay fever have shown that in 
dilutions of one in ten thousand, when placed in the eyes or nose, 
typical attacks of hay fever have been produced, in which the 
symptoms are as irregular and peculiar as in a natural attack. The 
use of the antitoxin in these artificial cases promptly checks the 
symptoms and causes the attack to disappear. In the case of in- 
dividuals not subject to hay fever the toxin had no effect whatever. 
An antitoxin has been prepared by Dunbar, combining pollen from 
spring plants and fall grasses, and has been experimented with with 
satisfactory results. Summarizing the experience of ten years' use 
of pollen antitoxin, the following conclusions were reached: " 1. 
The serum produces prompt and positive amelioration of the symp- 
toms of hay fever in the majority of cases. 2. In a smaller number 
this is accompanied with complete disappearance of the affection for 
that particular season. 3. When results are obtained, it favorably 
influences all the manifestations of hay fever in the larger number 
of cases, while in a smaller class one or more of the symptoms seem 
to be most markedly influenced. 4. When given during the attack 
of hay fever, irrespective of its severity, it produces palliation rather 
than absolute cure. 5. When successfully used during one season, 
it does not prevent the reappearance of the disease the following 
season, although there is reason to believe that a slight influence in 
modifying further attacks does exist." 

Philip F. Fackenthall. 



THE U S. PHARMACOPOEIA IX. 

Prof. Joseph P. Remington, chairman of the Committee of Re- 
vision, in a recent address before the New York Branch of the 
A. Ph. A., stated that the work of revision was fast approaching com- 
pletion and that the book would soon be printed. By international 
agreement it will contain the same strength and doses for all power- 
ful preparations as do many of the leading pharmacopoeias of the 
world. Tentatively, there will be 798 articles in the new U. S 1 . P. 



THE AMEEIOAN 



JOURNAL OF P H ASKMA Y 



From the Division of Pharmacology, Leland Stanford Jr. University. 

After having discovered the pressor action of the extracts of the 
adrenal glands, Oliver and Schaefer 1 studied the action of those 
made from other ductless glands. They found that aqueous or 
glycerine extracts of sheep pituitaries, on intravenous injection into 
certain animals, caused a persistent rise in blood-pressure, usually, 
but not always, associated with a slowed heart-rate. This rise oc- 
curred even in animals with the medulla destroyed, and perfusion 
experiments proved the action to be mainly peripheral. An increase 
in the force of the heart action is partly responsible for this rise, 
as extracts of pituitary glands act directly on the muscle-fibres of 
the vessels and heart. The pressor action is especially marked in 
cases of artificially lowered blood-pressure. 

The few experiments which Szymonowicz 2 made suggested that 
extracts of this organ caused a fall in blood-pressure with a rapid 
heart-beat, the opposite condition to what Oliver and Schaefer 
found. Silvestrini 3 merely noted a fall in blood-pressure, and this 
seemed to be the characteristic reaction. According to von Cyon, 
there are two compounds : one which slows and strengthens the 

1 Oliver, G., and Schaefer, E. A., " On the Physiological Action of Ex- 
tracts of' Pituitary Body," Jour, of Physiology, vol. 18, p. 277 (1895). 

2 Szymonowicz, L., " Die Function der Nebennieren," Archiv. f. Physiol, 
vol. 64, p. 131 (1896). 

3 Silvestrini, R., " Sull' azione dell' estratto aquoso del lobo posteriore dell' 
ipofisi sulla pressione sanguinea," Rcvista critica di din. mcd., No. 28, 1905, 
seen only in reference. 



CONTRIBUTION TO THE CHE^&|^Y ^\%HE 
PITUITARY PRESSOR COMPtTTO^>5^' 




By Albert C. Crawford and Zeno Ostenberg, 



1291) 



292 



Chemistry of Pressor Compounds. { Am j°™' ilu rm " 



heart, while the other causes a rise in blood-pressure through inhi- 
bition of the depressor nerve. 4 

Howell traced the pressor action of the pituitary exclusively to 
the infundibular portion, and found that, if the injection of extracts 
of this portion were repeated rapidly, the second injection caused 
no rise in blood-pressure and produced no cardiac inhibition. He 
also found that extracts of the anterior lobe usually induced no 
effect, either on the blood-pressure or on the heart- rate. If the 
vagi were intact, as in Oliver and Schaefer's original experiments, 
extracts of the infundibular lobe caused a rise in blood-pressure 
with a slow heart-beat, but if the vagi were cut there was a rise in 
pressure with less slowing than when the vagi were intact, hence the 
action is partly central. Other workers have found that some of 
the cardiac slowing is peripheral in origin. 6 

In Howell's experiments both sheep and dog pituitaries were 
used and were tested on dogs. Schaefer and Vincent 7 confirmed 
Howell's conclusions that the pressor principle was confined to the 
infundibular portion, and the latter workers made the further sug- 
gestion that in extracts of this gland there was a depressor com- 
pound. They agreed with Howell that a second injection, if given 
too soon after the first, would cause no immediate rise in blood- 
pressure, but claimed there might be a delayed rise and that the 
second injection produced a more marked fall, so that no tolerance 
to the depressor action was produced. The depressor action still 
occurred after the use of atropin and was, therefore, not due to 
cholin. Slowing of the heart was not constant, but when present 
might be very persistent. 

They found that the pressor compound, at least in the form in 
which it existed in the glands, was insoluble in alcohol or ether, 
while the depressor body was soluble in absolute alcohol. Schaefer 

4 Cyon, E. v., " Die physiologischen Herzgiften," Arch. f. ges. Physiol., 
vol. 73, p. 339 (1898). 

5 Howell, W. H., " Physiological Effects of Extracts of the Hypophysis," 
Jour. Exper. Med., vol. 3, p. 245 (1898). 

6 Hebdom, K., " Ueber die Einwirkung verschiedener Stoffe auf das 
isolierter Saugetierherz," Skan. Arch. /. Physiol., vol. 8, p. 147 (1898) ; Cleg- 
horn, A., " Action of Animal Extracts ... on Mammalian Heart 
Muscle," Amer. Jour. Physiol., vol. 2, p. 273 (1899). 

7 Schaefer, E., and Vincent, S., " Physiological Effects of Extracts of the 
Pituitary Body," Jour. Physiol., vol. 25, p. 87 (1899). 



Am * ju?y r "iS.4 arm * } Chemistry of Pressor Compounds. 293 

and Herring 8 found little or no rise in blood-pressure if the pitui- 
tary extracts were given animals by mouth, but believed the com- 
pound which gave immunity was still absorbed, because the depressor 
effect of intravenous injections was more marked if given after the 
oral use of such extracts. They state that a very small dose ( 1 c.c. 
of a 1 per cent, extract) does not produce immunity, although the 
rise in blood-pressure which follows a second injection is less than 
that which follows the first. In this connection it is interesting to 
note that Biedl 9 and also Cushing have found that removal of the 
posterior lobe is borne by dogs apparently with slight danger to 
life, whereas removal of the anterior lobe will cause death within 
a few days; also Ott and Scott 10 have found that the injection of 
extracts of the posterior lobe will cause a diminution in size of the 
thyreoid gland, but that extracts of the anterior lobe will cause 
enlargement of this gland. 

In Hamburger's experiments extracts of the anterior lobe caused 
a fall in blood-pressure with weakening of the heart and accelera- 
tion of the rate, while a second injection, if given early, produced 
no effect on the blood-pressure, although if the interval between 
injections was longer a fall still occurred. At the autopsy of one of 
Biedl's animals, similarly injected, there was widespread clotting. 11 

The fall from injection of extracts of the anterior lobe is more 
marked in atropinized animals, but Biedl 12 does not consider the 
fall produced by extracts of the anterior lobe as characteristic. 
Hamburger noted that a secondary rise at times followed the depres- 
sion caused by the injection of extracts of the anterior lobe. 13 

fknile-Weil and Boye 14 claim there is a further difference be- 
tween the action of extracts of the anterior and of the posterior 



8 Shaefer, E., and Herring, P. T., " Action of Pituitary Extracts upon the 
Kidney," Philos. Trans. Roy. Soc. London, Ser. B, vol. 199, p. 1 (1908). 

9 Biedl, A., " Innere Sekretion," vol. 2, p. 116. 

10 Ott, I., and Scott, J. C, " Effect of Animal Extracts and Iodine upon 
the Volume of the Thyroid Gland," Thcrap. Gaz., vol. 37, p. 781 (1913). 

11 Biedl, /. c, p. 141. 

12 Biedl, /. c, p. 141. 

13 Hamburger, W. W., "Action of Intravenous Injections of Glandular 
Extracts," Amer. Jour. Physiol., vol. 11, p. 282 (1904). 

14 £mile-Weil, P., and Boye, G., " Action differente des lobes hypophy- 
saires sur la coagulation du sang," Compt. rend. Hcb. Soc. dc Biol., vol. 67, 
p. 428 (1909). 



294 Chemistry of Pressor Compounds. { Am ' fui u y r * m * 

lobes, in that extracts of the latter favor coagulation of the blood, 
while those of the former do not. 

Paton and Watson 15 have found that extracts of the pituitary 
gland (pituitrin), when injected intravenously into birds, caused a 
fall in blood-pressure, and that after repeated injections this de- 
pressor action failed to appear, although, at times, .such injections 
caused a rise in blood-pressure. In birds the fall in pressure was 
due to dilatation of the abdominal vessels, and might be neutralized 
by more powerful ventricular contraction. 

It has been recently shown that the effects of extracts of the 
pituitary gland depend to some extent upon how rapidly they are in- 
jected; thus Miller and Miller 10 state that " if a strong saline ex- 
tract of the posterior lobe of the hypophysis be injected rapidly a 
depressor effect only may be obtained, whilst if the injection be 
made slowly or in a very dilute form, the pressor effect predomi- 
nates." 

On purely histological evidence Herring 17 separated the pituitary 
gland into an anterior, a posterior, and an intermediary portion, and 
argued that the pressor principle originated in the pars intermedia. 
Recently Lewis, Miller and Matthews 18 have found that the more 
sharply the intermediary portion of the pituitary is removed and 
extracted, the greater the rise in blood-pressure which results from 
injection of such extracts, and the less of the pars intermedia is 
used the less the rise. Biedl claims that the pars intermedia can be 
removed comparatively easily in thyreoidectomized animals and that 
the injection of aqueous extracts of this portion of the gland causes 
a slowed heart with a rise in blood-pressure, while extracts of the 
pars nervosa, freed from the pars intermedia, are inactive, save in 
producing a slight fall. 

15 Paton, D. H., and Watson, A., " Actions of Pituitrin, Adrenalin, and 
Barium on the Circulation of the Bird," Jour of Physiol, vol. 44, p. 413 (1912). 

16 Miller, J. L., and Miller, E. M., " Effects on Blood-pressure of Organ 
Extracts," Jour, of Physiol., vol. 43, p. 242 (1911). 

17 Herring, P. T., " Histological Appearances of the Mammalian Pituitary 
Body," Quart. Jour. Phys., vol. 1, p. 1214 (1908). 

"Lewis, D., Miller, J. L., and Matthews, S. A., "Effects, on Blood- 
pressure of Various Anatomical Components of the Hypophysis," Archives of 
Int. Med., vol. 7, p. 785 (1911). See also Schickele, G., " Ueber die Herkunft 
der blutdrucksteigernden Substanz in der Hypophysis," Zcits. f. gesam. Med., 
vol. 1, p. 545 (1913). 



Am "ju°iy r 'i9i4 arm *} Chemistry of Pressor Compounds. 29$ 

Lewis, Miller and Matthews believe the pars intermedia to be 
separated by the hypophyseal cleft into one portion closely con- 
nected with the anterior lobe and one with the posterior. This may 
explain why a rise in pressure may follow the injection of extracts 
of either lobe. They obtained a rise in pressure more frequently 
from injections of extracts of the anterior lobe than from those of 
the posterior. Schaefer and Herring were inclined to the view that 
the activity of the anterior lobe might really be due to postmortem 
infiltration. 

Lewis, Miller and Matthews found that after removal of the 
depressor compound, extracts of the pars intermedia caused a rise 
in blood-pressure without slowing of the pulse-rate. They, like 
Howell, also noted that extracts of the posterior lobe caused a rise 
in blood-pressure, which was followed by a fall, and that there was 
then a return to the higher level. This fall after the primary rise 
was only seen when extracts of the posterior lobe were used, and 
they attributed this to a second depressor principle which was in- 
soluble in alcohol. 

Osborne and Vincent 19 found that the pituitaries of various 
teleostean fishes exerted a pressor action, and claimed that the cen- 
tral part of the infundibular portion of the ox pituitary had more 
pressor activity than the peripheral portion. In a recent compara- 
tive study of the pituitary gland Herring sums up the work as 
follows : " The presence of active physiological principles in the 
pituitary is associated with a tissue of nervous origin, 1 ' and " there 
is reason to believe that the granules are the histological represen- 
tatives of the active principles, and that they are the products of 
part of the epithelial lobe — the cells of the pars intermedia — carried 
to, elaborated in, and stored by, the pars nervosa." 

Vincent and Sheen 20 took the position that pressor principles 
could be found not only in the pituitaries and suprarenals, but in 
greater or less extent in most tissues, and that boiling the extracts 



19 Osborne, W. A., and Vincent, S., "Contribution to the Study of the 
Pituitary Body," Brit. Med. Jour. (1900), vol. 1, p. 502. 

20 Vincent, S., and Sheen, W., "Effects of Intravascular Injections of 
Extracts of Animal Tissues," Jour, of Physiol., vol. 29, p. 242 (1903). See 
also McCord, C. P., " Investigation of the Depressor Action of Pituitary 
Extracts, Archives of Int. Med., vol. 8, p. 609 (1911) ; Berlin, E., " Hemocholin 
und Neosin," Zcits. f. Biol., vol. 57, p. t (1911). 



t 



296 Chemistry of Pressor Compounds. { Am 'j^y r i9H arm ' 

made from these organs usually enhanced the depressor action and 
masked the pressor effects. Miller and Miller found that, by auto- 
clave treatment, the pressor action of pituitary extracts disappeared, 
while the depressor persisted. 

It has been shown 21 that in cats the injection of extracts of 
pituitary glands, taken from almost any vertebrate animal, will 
increase the urinary secretion. This action has been claimed by 
some 22 to be due to its pressor principle, but there is physiological 
evidence to show that the diuretic and pressor actions are due to 
separate constituents. This diuretic action is confined to the pos- 
terior lobe, and second injections of such extracts do not produce 
tolerance to its diuretic effect, but rather increase its action. Ex- 
tracts of pituitary glands taken from some animals have little or 
no effect on blood-pressure, yet exert a diuretic action. 23 

It has been found that extracts of pituitary glands exert an 
action on various organs which are supplied with unstriated muscles, 
such as the uterus, 24 intestines, bladder, etc. Recently Barger and 
Dale have shown that various amines will not only produce a rise 
in blood-pressure, but also affect various organs with unstriated 
muscles. In this case the action is on the extreme terminals (re- 
ceptor bodies) of the sympathetic nerves supplying these organs, 
and these observers have designated this action as " sympathomi- 
metic." In the case of the pituitary extracts the action, at least on 
the uterus, seems to be different, and is believed by Dale to be on 
the muscles rather than on the sympathetic nerve-endings. This 
view is supported by the experiments of Paton and Watson on 
birds. 

The pressor principle and the one which causes uterine contrac- 
tions may not necessarily be the same, or, at least, all of the uterine 

21 Schaefer, E. A., and Herring, P. T., " Action of Pituitary Extracts 
upon the Kidney," Philos. Trans. Roy. Soc. London, Ser. B, vol. 199, p. 1 
(1908). 

22 Houghton, E. M., and Merrill, C. H., " Diuretic Action of Adrenalin 
and the Active Principle of the Pituitary Body," Jour. Amer. Med. Assoc., 
vol. 51, p. 1849 (1908). 

23 Herring, P. T., " Further Observations upon the Comparative Anatomy 
and Physiology of the Pituitary Body," Quart. Jour. Exper. Physiol., vol. 6, 
P- 73 (1913). 

24 Bayer, G., and Peter, L., " Zur Klenntniss des Neurochemismus der 
Hypophyse," Arch. f. exper. Path., vol. 64, p. 204 (1911). 



Am.^jour^Pharm. j Chemistry of Pressor Compounds. 297 

action may not be due to the pressor principle. Engeland and 
Kutscher 25 have attempted to isolate the compound which causes 
contractions in the cat uterus. They attributed this action to cholin, 
as they isolated this base from pituitaries and found that control 
solutions of cholin caused contractions of the isolated uterus. Gau- 
trelet had previously found cholin in the hypophysis. Engeland 
and Kutscher believe the pressor principle to be -different from the 
one which acts on the uterus. 

Bayer and Peter 26 claim that the pituitary principle which stim- 
ulates the autonomic nerve-endings of the intestines resides in the 
posterior lobe only and is not specific for this organ, and that the 
portion of the lobe insoluble in alcohol causes inhibition, while the 
portion soluble in alcohol causes increased activity. On isolated 
bronchial muscle, extracts of the hypophysis, histamine, and Witte's 
pepton caused no contraction. 27 

Like the secretion of the ovaries, extracts of the pituitary glands 
also increase the secretion of the mammary gland. 28 According to 
Herring, 20 extracts of the pituitary gland of skates produce an 
increase in mammary secretion, but do not produce a rise in blood- 
pressure or increase in urinary secretion. 

The apparent similarity 30 in some of the actions of pituitary ex- 

25 Engeland, R., and Kutscher, F., " Ueber einige physiologischen wichtige 
Substanzen," Zeits. f. Biol., vol. 57, p. 527 (1912) ; Schickele, G., "Ueber die 
Herkunft der blutdrucksteigernden Substanz in der Hypophysis," Zeits. f. 
d. ges. exp. Med., vol. 1, p. 545 (1913) ; Bell, W. B., "Pituitary Body," Brit. 
Med. lour. (1900), vol. 2, p. 1609. 

26 Bayer, G., and Peter, L., " Zur Kenntniss des Neurochemismus der 
Hypophyse," Archiv. f. exper. Path., vol. 64, p. 204 (1911). 

27 Trendelenburg, P., " Physiologische und pharmakologische Untersuch- 
ungen an der isolierten bronchial Muskulatur," Archiv. f. exper. Path., vol. 
69, p. 106 (1912). 

28 Ott, L, and Scott, J. C., Proc. Soc. Exper.. Biol, vol. 1, p. 1911) ; 
Schaefer, E. A., " On the Effect of the Pituitary and Corpus Luteum Ex- 
tracts on the Mammary Secretion in the Human Subject," Quart. Jour. Exper. 
Physiol, vol. 6, p. 17 (1913) ; Gavin, W., "On the Effects of Administra- 
tion of Extracts of Pituitary Body and Corpus Luteum to Milch Cows," 
ibid., p. 13. 

20 Herring, P. T., " Contribution to the Comparative Physiology of the 
Pituitary Body," Quart. Jour. Physiol, vol. 1, p. 261 (1908). 

30 Claude, H., and Baudoin, A., " Sur les effets de certains extraits hypo- 
physaires," Comp. rend. Acad, des Sci. Paris, vol. 153, p. 1513 (1911) ; v. 
Frankl-Hochwart, L., and Frohlich, A., " Zur Kenntniss der Wirkung des 
Hypophysins," Archiv. f. exper. Path., vol. 63, p. 347 (1910). 



298 Chemistry of Pressor Compounds. { Am j l f 1 y" r i 9 H arm * 

tracts with those of epinephrin suggested the identity, or at least a 
close chemical relationship of the pressor principle of the pituitary 
with that of the adrenal glands, hut Allers and Houssay 31 proved 
that the chemical reactions of pituitary pressor extracts were dif- 
ferent from those of epinephrin, and the method used for isolating 
epinephrin from the suprarenal glands failed to yield this compound 
when tried on pituitary extracts. Meyers 32 has shown that, while 
repeated intravenous injections of epinephrin produced arterial 
degeneration in rabbits, pituitrin caused almost no vascular changes ; 
and Cramer 33 has claimed that, while epinephrin when mixed 
with formaldehyde rapidly lost its pressor activity, Pituitrin when 
so treated retained this activity. Again, Meltzer 34 claims there is a 
difference in action on the enucleated eye between epinephrin and 
the commercial preparation of pituitary glands. Allers noted that 
Pituitrin, which is a dilute acetic extract of the glands, gave, like 
epinephrin, when treated with an alkali, an odor of an alkylamin. 
Fiihner 35 has recently stated that B-iminazolylethylamine hydro- 
chloride, or Histamin, when injected intravenously into rabbits, pro- 
duces the same effects on blood-pressure and the respiration as 
Pituitrin, but admits it is not the active principle of the pituitary 
gland, as this substance is more toxic than a corresponding amount 
of Pituitrin, and while repeated injections of B-iminazolylethyla- 
mine will give some tolerance to the injections of the same, yet will 
not give immunity to Pituitrin, so that at one time Fiihner suggested 
that the active principle of the pituitary gland is not B-iminazolyle- 
thylamine, but related to it. However, Einis 36 found that the. action 



31 Allers, R., " Zur Kenntniss der wirksamen Substanz in der Hypo- 
physis," Munch, med. Woch., vol. 56, pt. 2, p. 1474 (1909) ; Houssay, B. A. 
"' Estudios sobre la accion de los cxtractos hipofisiarios," p. 159. 

32 Meyers, M. K., " Die Wirkung von intravenosen Injektionen von Hypo- 
physenextrakt," Cent. d. Allg. Path., vol. 20, p. 109 (1909) ; Etienne and 
Parrisot, Arch, de med. Expcr., July, 1908, found slight lesions. 

33 Cramer, W., " On the Inactivation of Adrenalin in vitro and in vivo," 
Proc. Physiol. Soc, p. xxxvi ; Jour, of Physiol., vol. 42 (1911). 

34 Meltzer, S. J., " Influence of the Infundibular Portion of the Hypophy- 
sis upon the Pupil," Proc. Soc. Expcr. Biol., vol. 9, p. 103 (1912). See also 
Kepinow, p. 261. 

35 Fiihner, H., " Das Pituitrin und seine wirksamen Bestandteile," Munch, 
med. Woch.. vol. 59, p. 852 (1912) ; Kaufmann, P., "Ueber den Einfluss der 
Organextrakte auf die Blutgefasse," Zcit. f. Physiol, vol. 27, p. 532. 

36 Einis, W., " Ueber die Wirkung des Pituitrin und B-imidazolylethyl- 
amine auf die Herzaktion," Biochcm. Zeits., vol. 52, p. 96. 



Am 'juiy r 'i^4 arm '} Chemistry of Pressor Compounds. 299 

of B-iminazolylethylamine on the frog heart was different from that 
of Pituitrin. It is difficult to understand how this substance could 
be the active pressor constituent of the pituitary glands, because in 
carnivora it produces a fall in blood-pressure, although it produces 
a rise in pressure in herbivora, while pituitary extracts cause a rise 
in rabbits and dogs. 37 

Kepinow has pointed out a synergism between the action of epine- 
phrin and pituitary extracts; that is, small doses of epinephrin are 
claimed to increase the action of pituitary extracts so that the com- 
bined action corresponds to more than their simple addition. Small 
inactive doses of extracts of the hypophysis increase the action of 
epinephrin on rabbits ; in other words, the animal becomes sensi- 
tized. 38 

Chemical Experiments. 

Considerable chemical work has been done on the pituitary 
glands, but apparently no pure pressor compound has as yet been 
definitely isolated. Calcium, phosphorus, bromine, arsenic, guanin, 
and cholin have been found to occur in the glands, and, while iodine 
was suspected, owing to an apparent histological resemblance be- 
tween the thyreoid and pituitary glands, as yet it has not been proved 
to be present. 

According to our experiments, repeated evaporation of extracts 
of the pituitary gland, and also putrefaction, will cause rapid dimi- 
nution in pressor activity. Schaefer and Herring 39 noted that 
trvptic digestion for 18 hours did not destroy its diuretic or pressor 
action, and that peptic digestion, while it did not injure its diuretic 
action, changed the character of the pressor action. 

Oliver and Schaefer found that aqueous extracts of pituitary 
glands could be boiled, at least for a short time, with little or no loss 
in pressor activity. Aldrich 40 extracted the fresh infundibular por- 
tion of the gland with dilute acetic acid and then removed the coag- 

37 Dale, H. H., and Laidlaw, P. P., " Physiological Action of B-iminaz- 
olylethylamine," Jour. Physiol., vol. 41, p. 318 (1910-11). 

38 Kepinow, " Ueber den Synergismus von Hypophysis Extrakt und Adre- 
nalin," Arch. f. expcr. Path., vol. 67, p. 247 (1912). 

:!n Schaefer and Herring, /. c, p. 22. 

40 Aldrich, T. B., " Preliminary Contribution to the Chemistry of the 
Infundibular Portion of the Pituitary Body," Amer. Jour. Phys. (1907-08), 
vol. 21, p. xxiii. 



300 Chemistry of Pressor Compounds. { Am '/ U iy r 'i 9 1 i4 arm ' 

ulable proteins by means of heat and nitration. Aqueous extracts 
of undried pituitaries pass through filter paper with the greatest 
difficulty, but after thorough coagulation of the proteins the extracts 
filter readily. 

As Lewis, Miller and Matthews showed that a pressor action 
could be obtained from all portions of the gland, we used the whole 
gland and avoided the tedious mechanical labor of removing the 
posterior portion. The fresh beef glands were ground in a meat- 
chopper and extracted twice with o.i per cent, acetic acid, and, after 
squeezing through cheese-cloth, the extract was coagulated on the 
water-bath and the filtrate evaporated in vacuo. This gradually 
colored during evaporation and left a brownish-yellow, gummy, non- 
crystalline mass, which, on intravenous injection into dogs, would 
induce a marked rise in blood-pressure. * 

On treatment with hot methyl alcohol (Merck's highest purity) 
all the color and activity went into the alcohol. This solution gave 
a heavy precipitate on the cautious addition of a drop or two of con- 
centrated sulphuric acid, which redissolved with an excess of the 
acid. This precipitate dissolved in water, forming a reddish solu- 
tion, and produced a marked rise in blood-pressure. When freshly 
precipitated it dissolved in hot methyl alcohol or ethyl alcohol (com- 
mercial 95 per cent.), but if washed with ether and placed in the 
desiccator became insoluble in either alcohol. At first we believed 
this to be a true sulphate mixed with calcium, but found that 
after further purification it failed to be reprecipitated from methyl 
alcohol by sulphuric acid, hence we argued that the first precipita- 
tion was merely mechanical. This precipitate, dissolved in water, 
or the acetic-acid extract of the glands, gave a heavy precipitate 
with lead acetate or lead subacetate, mercuric chloride or uranium 
acetate. 

The filtrate after uranium acetate precipitation was active, but 
uranium gave no precipitate if the lead precipitation had been com- 
pletely done. Mercuric chloride also gave a heavy precipitate and 
the filtrate was active. Gold chloride, platinum chloride, silver 
acetate, picric acid, picolinic acid, and benzoyl chloride with 
sodium hydrate, all gave precipitates with a solution of the sulphuric- 



* Note. — These dogs were narcotized with ether and morphine and the 
vagi nerves were usually cut. The most satisfactory results were obtained 
by using young dogs. Older or large ones did not seem to respond well. 



Am 'jSy r 'i9i4 arm '} Chemistry of Pressor Compounds. 301 

acid-alcohol precipitate, or from the acetic acid extract of the glands, 
but as yet we have been unable to obtain an active pressor compound 
from any of these precipitates. Aldrich claims to have obtained an 
active crystalline picrate by precipitation with picric acid from a 
concentrated solution of the glands purified by precipitation with 
uranium acetate, but he has published no analyses of this picrate. 

We found that sodium tungstate gave an active precipitate which 
was soluble in acetic acid, but a control solution of sodium tung- 
state also caused a rise, hence we cannot say whether or not the 
activity was due to the reagent. We have been unable to throw out 
an active base by means of alkalies, or any active combination of 
it by means of aluminum hydroxide, but obtained an amine odor on 
treatment of active solutions with an alkali. Magnesium oxide 
seemed to carry down mechanically some of the pressor compound. 
No active volatile compound was obtained by alkaline distillation. 

A marked odor of skatol arose on treating Pituitrin with hydro- 
gen peroxide, and the solution lost its pressor action. Schaefer and 
Herring state that extracts of the pituitary glands, when treated 
with this reagent, still induced an increased urinary secretion, but 
produced merely a slight rise in blood-pressure. In their experi- 
ments reducing agents, such as zinc and hydrochloric acid, were 
without effect, either on the diuretic or on the pressor action of such 
preparations. 

Recently Baudouin 41 claims that he has obtained an ash- free, 
hygroscopic compound by dissolving the dried acetic acid extract in 
absolute ethyl alcohol and freezing out the active substance. From 
methyl alcohol solution of the acetic acid extract we succeeded in 
freezing out, by means of solid carbon dioxide, an almost white 
precipitate which caused a marked rise in blood-pressure, and the 
filtrate was only slightly active, but on resolution of this active pre- 
cipitate, freezing gave no precipitate. 

After precipitating with lead subacetate and removing as much 
of the lead as possible by phosphoric or sulphuric acid the filtrate 
was still active, even though hydfogen sulphide was used to remove 
the last? traces of lead ; but if hydrogen sulphide alone was used to 
remove the lead, both the filtrate and precipitate became inactive, 
but solutions of the glands to which lead had not been added were 



41 Baudouin, A., " Sur le recherche du principe actif de l'hypophyse," 
Comp. rend. Soc. de Biol, vol. 74, p. 1138 (1913). 



302 Chemistry of Pressor Compounds. { Am 'jui° y ur i9i4 arm ' 

uninjured by hydrogen sulphide alone, hence the active pressor com- 
pound must have been carried down with the lead sulphide, but 
as yet we have been unable to recover it from the lead sulphide pre- 
cipitate. From this precipitation and from the fact that it is com- 
pletely removed or destroyed by animal charcoal we argued a high 
molecular weight, although this does not necessarily follow. After 
thorough precipitation with lead subacetate and freeing from lead 
with phosphoric acid the filtrate gave no biuret reaction, but gave a 
reaction with Folin's hydroxy-phenyl reagent. After lead-sub- 
acetate precipitation and removal of the lead, neither zinc sulphate 
nor ammonium sulphate (saturated solution) gave a precipitate. 

In connection with one of our students we had begun some work 
with Caviar pepton * and found that the intravenous injection into 
a dog of a few milligrams of it would produce a marked and per- 
sistent rise in blood-pressure. This at once suggested that there 
was a pepton which would cause a rise in blood-pressure, or that the 
rise which followed the injection of Caviar pepton was due to cal- 
cium or barium, supposedly used in neutralizing the acid used in the 
hydrolysis, or to amino-compounds arising in the formation of the 
pepton, or to albumose, or to some other unknown compound formed 
along with peptons. 

We had noticed that an iodine and potassium iodide solution 
would produce a precipitate from certain pituitary extracts, and that 
this precipitate, after decomposing with sulphurous acid, was physio- 
logically active, while Fiihner has shown that various active prin- 
ciples were obtained from the phosphotungstic acid precipitate, and 
Aldrich has obtained an active principle by means of picric acid. 

Now certain so-called peptons give precipitates with phospho- 
tungstic acid, iodine and potassium iodide solution and picric acid, 
and produce an immunity, or rather a tolerance, to a second injec- 
tion and interfere with coagulation of the blood. Pick and Spiro 42 
showed that the depressor action on blood-pressure and the anti- 
coagulant action of Witte's pepton were not due to peptons or albu- 
moses, but to some other compound associated with them; as Pick 



* Note. — Supplied by the courtesy of the Hoffmann-La Roche Chemical 
Works of Grenzbach, Germany, through their New York branch. 

42 Pick, E., and Spiro, K., " Ueber gerinnunghemmende Agentien," Zeits. 
f. Physiol. Chem., vol. 31, p. 235 (1900). 



Am ' jS r 'i9i4 arm ' } Chemistry of Pressor Compounds. 303 

says, " Es gibt Peptone ohne Peptonwirkung unci Peptonwirkung 
ohne Peptone." A number of so-called peptons produce eosinophilia 
in varying degrees. In some cases of acromegaly, a disease asso- 
ciated with pituitary disturbances, eosinophilia has been reported. 43 
Some pepton preparations induce symptoms similar to those 
which occur during the anaphylactic reaction. Biedl * 3a claims that 
Urechia's results with the intraperitoneal injections of pituitary 
extracts must be interpreted as an anaphylactic reaction, and Pan- 
kow 44 found that, after the intravenous injection of 1—5 c.c. of 
Pituitrin, rabbits became more sensitive to a second injection made 
in from 1 to 5 days after the first. According to Fiihner, the respi- 
ratory stoppage from Pituitrin resembles that from anaphylaxis. 45 
Extracts of the posterior lobe are said to accelerate coagulation of 
the blood, while those from the anterior lobe retard it. 46 Witte's 
pepton, especially the portion soluble in absolute alcohol, retards 
coagulation. 47 

The pituitary gland contains various enzymes, which might form 
pepton-like bodies. 48 

Paal, 49 by treating albumen with hydrochloric acid, has obtained 
products which he calls salts of pepton. These, unlike pepton, are 
soluble in alcohol. Schrotter 50 claims to have obtained similar com- 
pounds with albumoses. Peptons consist mainly of mono-amino 
acids, and, according to De Waele, the pepton action is primarily 



43 Falta, W., "Die Erkrankungen der Blutdrusen," 1913, p. 212. 

43a Biedl, " Innere Sekretion," vol. 2, p. 133 (1913) ; Urechia, C. J., " Action 
de l'extrait hypophysaire en injections intraperitoneales," Comp. rend. Soc. 
de Biol, vol. 65, p. 278 (1908). 

44 Biedl, /. c., vol. 2, p. 136. 

45 Fiihner, /. c., p. 406. 

40 £mile-Weil, P., and Boye, G., " Action differentes des lobes hypophy- 
saires sur la coagulation du sang," Comp. rend. Soc. de Biol., vol. 67, p. 
428 (1909). 

47 Zunz, E., "Apropos de Taction anticoagulante des injections intra- 
veineuses de peptone de Witte," Comp. rend. Soc. de Biol, vol. 73, p. 50 
(1912). 

48 Buetow, " Zur Kenntniss der Hypophysenzyme," Biochem. Zeits., vol. 54, 
p. 40 (1913). 

49 Paal, C, " Ueber die Peptonzalze des Eieralbumine," Ber. d. dcutsch. 
chem. Gesells., vol. 27, p. 1845. 

60 Schrotter, Monats. f. Chemis., vol. 14, p. 612 (1893). 



304 Chemistry of Pressor Compounds. { Am 'ju?v r 'i^i4 arm ' 

an amino action. From Witte's pepton Pick 51 claims to have sepa- 
rated two peptons and four albumoses. However, as Haslam points 
out, the methods do not give sharp separations. 52 Pick precipitated 
the primary albumoses by means of ammonium sulphate, and sepa- 
rated them by alcohol ; the hetero-albumoses 53 being precipitated by 
weak ethyl alcohol, while the proto-albumoses remained in solution 
with rather strong alcohol. The hetero-albumoses would precipi- 
tate on dialysis, and long heating converted them into an insoluble 
compound (dysalbumid) . Witte's pepton contained very little 
of the proto-albumoses. After ammonium sulphate precipitation 
the filtrate yielded a product which was called albumose C. On 
treating the hetero-albumoses 54 with hydrochloric acid no tyrosin 
was obtained, but large amounts of leucin were found, while oxida- 
tion with potassium permanganate yielded a compound believed to 
be phenyl-amino-propionic acid. The proto-albumoses yielded 
tyrosin and gave a marked skatol odor on decomposition. Pick's 
hetero-albumose contained no indol nucleus, but yielded large 
amounts of di-amino compounds. 

In one experiment Pick noted that both the proto-albumoses and 
hetero-albumoses obtained from Witte's pepton caused a rise in 
blood-pressure, but as these albumoses had been prepared by the 
ammonium sulphate method the rise may have been due to some of 
the precipitant, However, another dog merely responded by a fall 
in blood-pressure when hetero-albumose was injected, and in Popiel- 
ski's experiments proto-albumose, prepared by Pick's method, pro- 
duced a rise in blood-pressure in one case, but a fall in the second, 55 



r ' 1 Pick, E. P., " Zur Kenntniss der peptischen Spaltungsprodukte des Fi- 
brins," Zcits. f. physiol. Chem., vol. 28, p. 219 (1899) ; Bcitrag s. Chem. 
Physiol., vol. 2, p. 481 (1902). See also Zunz, E., "Die fractionirte Abscheid- 
ung der peptischen Verdauungsprodukte mittelst Zinksulfat," Zeits. f. 
physiol. Chem,, vol. 27, p. 219 (1899). 

52 Haslam, H. C, " Separation of Proteins," Jour. Physiol., vol. 36, p. 154 
(1907-08). 

53 Kiihne and Chittenden. 

54 Schulze, E., " Untersuchungen ueber die Amidosauren welche bei der 
Zersetzung der Eiweissstoffe durch Salsaure und durch Barytwasser ent- 
stehen," Zcits. f. physiol. Chem., vol. 9, p. 72. 

55 Popielski, L., " Ueber die Wirkungsweise des Chlorbaryium, Adrenalin 
und Pepton Witte auf den peripherischen vasomotorischen Apparat," Archiv. 
f. cxper. Path., Stipplementband 1908, p. 44 1. 



Am 'tjfiiy r \$A rm ' } Chemistry of Pressor Compounds. 305 

so that Popielski suspected barium to be present in one of the prepa- 
rations. 

Zunz 50 has also found that so-called hetero-albumose, thio- 
albumose, deutero-albumose, and, especially, proto-albumose pro- 
duced a rise in blood-pressure in dogs and rabbits. This rise was 
followed by a marked fall, but, in the case of the proto-albumoses, 
large amounts were necessary to produce the fall. Witte's pepton 
has been shown to exert both a vaso-constrictor and a vaso-dilator 
action. 57 Those products of digestion which gave no biuret test 
caused a marked fall in blood-pressure. These differences in re- 
sults may really be due to a difference in the kind of proto-albumose 
or hetero-albumose used, as we have no positive proof that all fibrin 
from which Witte's pepton is obtained has necessarily the same 
chemical composition. Proto-albumose and syn-albumose caused 
recovery of the exhausted isolated heart, while peptons caused sys- 
tolic stoppage. 

Loeper and Esmonet 58 have found that a weak solution of what 
is, called pepsin caused a slight fall in blood-pressure, followed by a 
rise. This rise was especially marked if the pepsin was treated 
with hydrochloric acid, and Popielski 59 noted that a hydrochloric 
acid preparation of the thymus gland would produce a rise in blood- 
pressure with a slowed heart, and, like pituitary preparations, pro- 
duced this rise even after section of the spinal cord. This substance 
was not precipitated by phosphotungstic acid, lead acetate, or by 
platinum chloride in alcoholic solution, but was precipitated from 
absolute alcohol by an absolute alcoholic solution of mercuric chlo- 
ride. 

From this data we argued that some of the pressor activity was 
due to a compound with high molecular weight ; that is, one closely 
allied to the proteins and which would not dialyse. Schaefer and 
Herring claimed that the pressor compound of the pituitary would 

56 Zunz, E., " Untersuchungen ueber die Wirkung von Albumosen auf 
Blutdruck und Atmung," Archives internat. de Physiol., vol. n, p. 73 ; " Ueber 
die Wirkung von Albumosen auf das isolierte ueberlebende Schildkroten 
Herz," Ibid., vol. 10, p. 290. 

57 Kaufmann, P., " Ueber die Wirkung des Witte-Peptones auf die Blut- 
gefasse," Zent. f. Physiol., vol. 27, p. 724 (1913). 

B8 Loeper and Esmonet, " Action vaso-tonique comparee des different pro- 
duite de secretion gastrique," Comp. rend. Soc. de Biol., vol. 70, p. 8 (1911). 

69 Popielski, L., " Ueber eine neue blutdrucksteigernde Substanz des 
Organismus," Zent. f. Physiol., vol. 23, p. 137 (1909). 



306 Chemistry of Pressor Compounds. { Am 'ji?y r iSi arm ' 

dialyse, hence was not a protein. Using toluol as a preservative, 
we lound tnat much of the color dialysed through heavy parchment 
paper,* and that this colored solution was usually, though not always, 
active, while the liquid in the dialyser was intensely active. In this 
connection it may be remembered that Handovsky and Pick showed 
that there is in the serum a vaso-constrictor substance which is not 
dialysable 00 and which is not a globulin. 

When our dialysate was collected in fractions, the last fractions 
were without activity, whereas the fluid within the dialyser was still 
very active, hence one of the pressor principles, perhaps the mother 
substance of the dialysable pressor principles, is non-dialysable. 
The depressor principle passes quickly into the dialysate. 

After long dialysis the residue in the dialyser gives a slight pre- 
cipitate with lead subacetate, none with mercuric acetate or a solu- 
tion of iodine in potassium iodide, but gives a precipitate with phos- 
photungstic acid or phospho-molybdic acid and with stannous chlo- 
ride or mercuric chloride. It also gives a strong biuret reaction. 

Fuhner claims to have separated from pituitary extracts by 
means of phosphotungstic acid precipitation and subsequent decom- 
position of the precipitate by means of barium hydrate various 
pressor compounds. On the other hand, Popielski claims that the 
pressor activity is in the phosphotungstic acid filtrate. 61 Now it has 
been found that phosphotungstic acid changes the chemical compo- 
sition of various compounds, 62 hence there is a possibility that phos- 
photungstic acid would split our non-dialysable compound into 
various amines. 

The active non-dialysable portion seems to correspond in some 
respects to the fraction separated by Raper under the name Ba. 63 

* Note. — Animal membranes cannot be used for dialysis, as we have 
found that the pressor principles are completely removed from the solution 
by them and cannot be recovered. 

60 Handovsky, H., and Pick, E. P., " Ueber die Entstehung vasokon- 
striktorischen Substanzen durch Veranderung der Serumkolloide," Archiv. 
f. exper. Path., vol. 71, p. 62 (1913). 

61 Fuhner, " Ueber die isolierten wirksamen Substanzen der Hypophy- 
sen," Deutsch. med. Woch., vol. 39, p. 491 (1913) ; Popielski, L., "Hypo- 
physis und ihre Praparate," Berl. klin. Woch., vol. 50, p. 1156 (1913). 

62 Van Laer, H., "Nature of Amylase," Bull. Acad. Roy. Belg., vol. 4, 
p. 13; quoted in Chem. Abstr., vol. 8, p. 510 (1914). 

63 Raper, H. S., " Zur Kenntniss der Eiweiss-peptone," Beitr. z. chem. 
Physiol, vol. 9, p. 168 (1907). See also Stookey, L. B., "Zur Kenntniss der 
Eiweisspeptone," Beitr. z. chem. Physiol, vol. 7, p. 590 (1906). 



Am Jul" r 'i9i4 arm ' } Determination of Phenolphthalein. 307 



A NEW METHOD FOR THE DETERMINATION OF 
PHENOLPHTHALEIN. 

By Dr. A. Mtrkin, Cincinnati, O. 

Since phenolphthalein has come into extensive use as an in- 
gredient of laxative medicines, frequent occasions arise for its rapid 
and accurate determination. A few methods have been proposed, 
but, with the exception of one (Pharm. Zentrb., 191 1, p. 1126), they 
are all gravimetrical, therefore troublesome and unreliable, because 
applied to an organic substance. 

In trying to find a volumetric method for its determination I 
took advantage of its property to form a well-defined oxime with 
hydroxylamine. This is the principle of Walker's method for 
carvone determination, and of Nelson and his estimation of a number 
of ketones, including camphor. 

I first followed closely the directions worked out by the above- 
mentioned authors, but without result. I then worked according 
to Friedlander, who first discovered the phenolphthalein oxime, but 
the results were still far from satisfactory. Finally the following 
method was discovered, the results of which are very accurate: 

1. Gramme phenolphthalein, 0.8 gramme hydroxylamine hydro- 
chloride, and 0.52 gramme 90 per cent, sodium hydroxide solution, 
finely powdered, are dissolved in 35 to 40 c.c. of absolute alcohol 
and boiled for two to three hours under a reflex condenser until the 
liquid turns yellow. The liquid is then diluted with water, trans- 
ferred to a 250 c.c. volumetric flask, 10 c.c. of 10 per cent. H 2 S0 4 
are added and the flask filled to the mark with water. 50 C.c. are 
taken for titration. First the acid is neutralized, using Methyl 
orange as indicator. Then the excess of hydroxylamine is titrated 
with N/10KOH, using phenolphthalein as indicator. A blank is 
run, using the same amounts of hydroxylamine, NaOH and alcohol, 
and boiled for the same length of time. The difference in the 
number of cubic centimetres of N/10 alkali used in the titration of 
the blank experiment and in the sample, multiplied by 316, gives the 
quantity of phenolphthalein. 

When applying the method to medicinal tablets, the tablets were 
placed in a cylinder and crushed under alcohol with a glass rod. 
The alcohol was decanted off through a filter into a volumetric flask 



308 Estimation of Morphine in Pills, Etc. { Am - j J ^ y r 'Ju rm - 

and the extraction and decantation continued until complete ex- 
traction was obtained. An aliquot part of the extract was then 
taken for the determination. 

The method gives very accurate results in the hands of a careful 
worker. The yellow color of the oxime does not interfere with the 
titration, as by proper dilution it colors the liquid only slightly. 

Tablets of phenolphthalein frequently contain milk sugar or 
cane sugar, but as cane sugar does not give an oxime with hydrox- 
ylamine, and as milk sugar is practically insoluble in absolute 
alcohol, they do not interfere with the reaction. In case, however, 
that the method should give too high a result, it is better to make a 
volumetric determination of sugar in order to be more sure. 



THE ESTIMATION OF MORPHINE IN PILLS, 
TABLETS, ETC.* 

By J. B. Williams. 

In a paper read before the last meeting of the Pharmaceutical 
section of the American Chemical Society Mr. A. D. Thorburn sug- 
gests the estimation of morphine in pills, tablets, etc., by making 
the aqueous solution alkaline and extracting with a mixture of 
phenyl-ethyl alcohol and benzene, partially evaporating the alka- 
loidal solution, extracting the residue with n/io acid and titrating 
back with n/io or N/50 alkali, using hematoxylin as indicator. 
This method has recently been tried out with the following results. 
Duplicate assays of a 2 per cent, solution of morphine sulphate, 
using 10 c.c. ( = 0.2 Gm. morphine sulphate or 0.1506 Gm. anhy- 
drous morphine alkaloid). 

^=0.1827 Gm. morphine sulphate = 91.35 per cent. 
5 = 0.1919 Gm. morphine sulphate — 95.95 per cent. 

The phenyl-ethyl alcohol mixture did not separate sharply even 
after standing two hours. The morphine is apparently not dissolved 
in the mixture, but appears to be held in suspension by it. N/50 
alkali was used in titration, but the end point with hematoxylin as 
indicator is not sharp or satisfactory. 



* Presented at the meeting of die American Chemical Society at Wash- 
ington, D. C, December, 191 1. 



Am 'jui7 r i9 P i4 arm ' } Estimation of Morphine in Pills, Etc. 309 

Two further assays of the same solution were made, but after 
adding the phenyl-ethyl alcohol and benzene mixture and shaking, 
the separators were allowed to stand over night. 

The morphine was precipitated through the liquid and on the 
sides of the separators. The crystals of morphine were washed of! 
with alcohol and the assay completed. A, using cochineal as in- 
dicator, gave 0.1872 Gm. morphine sulphate = 93.6 per cent. B, 
with hematoxylin as indicator, gave 0.1805 Gm. morphine sul- 
phate = 90.25 per cent. 2 c.c. n/io acid and 4 or 5 drops of cochi- 
neal were added to B and again titrated, giving 0.1841 Gm. morphine 
sulphate = 92.05 per cent. 

It was thought that perhaps by replacing the benzene in. the 
phenyl-ethyl alcohol and benzene mixture with benzene or petro- 
leum ether a sharper separation would be obtained. This was tried 
on a solution of 1 Gm. of morphine alkaloid and 50 c.c. n/io acid 
in 100 c.c. Ten cubic centimetres of this solution titrated direct 
showed the presence of 0.0981 Gm. morphine alkaloid. Ten cubic 
centimetres extracted by the above modified method, replacing the 
benzene with petroleum ether, gave a sharp separation but low re- 
sults, 0.08729 Gm. = 87.29 per cent, being obtained. 

Judging from the limited number of assays made, the method 
is unsatisfactory both as to accuracy, time required, and cost and 
availability of material. 

As above stated, the morphine does not seem to be dissolved in 
the phenyl-ethyl alcohol and benzene mixture — at least not in the 
quantity of solvent specified. 

The U. S. P. gives the solubility of morphine in alcohol as 1-168 
and in chloroform as 1-1800, but in a mixture of these two solvents 
it will dissolve far more freely than in either of them separately. 

In order to ascertain the relative solubility of the freshly-pre- 
cipitated alkaloid in these solvents, morphine sulphate was added 
in excess to alcohol, chloroform, and a mixture of alcohol 1 part 
and chloroform 2 parts, respectively. Sufficient ammonia was added 
to liberate the alkaloid, and the flasks shaken for two or three 
hours. Ten cubic centimetres of the filtered liquid were then evap- 
orated to dryness and the alkaloid estimated volumetrically as crys- 
talline morphine. The averages of several estimations, weight to 
volume, were as follows : 



310 Estimation of Morphine in Pills, Etc. { Am ' Jl 'J 1 ; J ir i 9 u arm - 

Solvent. Wt. of cryst. morphine in 10 c.c. Solubility w-v. 

Alcohol 0.0547 Gm 1-182.6 

Chloroform 0.0110 Gm 1-909 

Alcohol 1 ) r . > n s 

~ U1 r \ 0-1316 Gm 1-76 

Chloroform 2 J 

The solubility of precipitated morphine crystals (dried below 
6o° C.) in the same solvents was also determined, the average of a 
number of estimations being : 

Solvent. Wt. of cryst. morphine in 10 c.c. Solubility w-v. 

Alcohol 0.0421 Gm 1-237.5 

Chloroform 0.0025 Gm 1-4000 

Alcohol 1 1 .0 r o 

~, , , 0.1258 Gm 1-80 

Chloroform 2 J 

Also the solubility of crystalline morphine in mixtures containing 
varying proportions of alcohol and chloroform: 

Solvent. Wt. of cryst. morphine in 10 c.c. Solubility. 

Alcohol 1 I Q I Q m ^ ^ 

Chloroform I J 



Alcohol 1 
Chloroform 2 



\ 0.1258 Gm 1-80 



Alcohol 1 1 o o879 Gm 1-114 

Chloroform 4 J 



Alcohol 1 
Chloroform 8 



.0.512 Gm I-I95.5 



Based on these experiments, the following assay method is 
recommended : 

A number of pills or tablets, or a quantity of the sample for 
assay containing not more than 0.5 Gm. morphine (preferably from 
0.1 to 0.2 Gm.), is dissolved in a few cubic centimetres of acidulated 
water, either in a separator or in a beaker, and then transferred to 
a separator, keeping the volume of the liquid as small as possible 
(from 5 to 10 c.c.) ; add from 15 to 25 c.c. of mixture of alcohol 1 
part and chloroform 2 parts by volume and 2 or 3 c.c. of 10 per cent, 
solution of ammonia, or sufficient to make distinctly alkaline. 
Stopper the separator and shake well for 2 or 3 minutes. After 
separation, which usually takes place inside of a few minutes, draw 
off the chloroformic solution, filter through cotton, well wet with 
chloroform, into a wide-mouth flask or beaker of about 150 c.c. 
capacity. Repeat the extraction with two further like portions of 



Am juf y ?i'9i P 4 harm '} Estimation of Morphine in Pills, Etc. 311 

the alcohol chloroform mixture and then with three 10 c.c. portions 
of chloroform. 

Evaporate the alcohol chloroform solution on a water-bath under 
a current of warm air to dryness, add a few cubic centimetres of 
alcohol and again evaporate. Dissolve the residue in an excess of 
n/io acid and titrate back with N/50 alkali, using cochineal as in- 
dicator. Each cubic centimetre of acid neutralized by the alkaloid = 
0.0301 Gm. of crystalline morphine or 0.0376 Gm. morphine sulphate. 

Following are some of the results obtained by this method. A 
2 per cent, solution of morphine alkaloid was prepared and assayed. 

( 0.0976 Gm. = 97.6 per cent. 

"5 c.c. = 0.1 Gm. morphine gave { , ^ , ^ 

° . fi { 0.0976 Gm. — 97.6 per cent. 

,• f 0.1940 Gm. — 97.0 per cent. 

10 c.c. — 0.2 Gm. morphine gave J ^ * 

{ 0.1952 Gm. = 97.59 per cent. 

20 c.c. = 0.4 Gm. morphine gave { °-390i Gm. = 97.52 per cent. 

10.3901 Gm. = 97.52 per cent. 

A 2 per cent, solution of commercial morphine sulphate. 

j 0.09944 Gm. = 99.44 per cent. 

5 c.c. = 0.1 Gm. morphine sulphate gave....! ^ 

J . " ( 0.09944 Gm. — 99.44 per cent. 

^ u- 1 u j. f 0.1981 Gm. = 99.06 per cent. 

10 c.c = 0.2 Gm. morphine sulphate gave.... \ y ^ F 

{ 0.1981 Gm. = 99.06 per cent. 

20 c.c. = 0.4 Gm. morphine sulphate gave... j °-3932 Gm. = 98.3" per cent. 

I 0.3940 Gm. = 98.5 per cent. 

The quantity of solvent used in the extraction of this sample was 
the same in each case. 

Two weighed quantities of another sample of morphine sulphate 
0.0535 and 0.0560 Gm. gave 0.05395 and 0.05634 Gm. respectively 
when extracted. 

A quantity of morphine alkaloid (1 Gm.) was dissolved in ex- 
actly 50 c.c. n/io acid, then made up to 100 c.c. with distilled water ; 
of this solution two 10 c.c. portions were titrated and required for 
neutralization 8.7 c.c. and 8.7 c.c. of N/50 alkali, showing the pres- 
ence of 0.09813 Gm. of morphine in each. Two other 10 c.c. por- 
tions extracted by the above method, the residue dissolved in 5 c.c. 
n/io acid and titrated, required 8.7 c.c. and 8.8 c.c. of N/50 alkali 
to neutralize, corresponding to 0.09813 Gm. and 0.09752 Gm. re- 
spectively. 



312 



Estimation of Morphine in Pills, Etc. { Am - ^ 



Several other samples of morphine sulphate and morphine alka- 
loid gave equally good results. A large number of pills and tablets 
assayed by this method gave results approximating closely the theo- 
retical content. 

The advantages of this method are accuracy, simplicity, and 
shortness of time required for completion, duplicate assays being 
easily completed inside of two hours, except when, owing to the 
presence of sugar or gummy matter in the sample, slight emulsions 
may form, requiring a little more time for separation, although this 
can usually be prevented by keeping the aqueous portion to as small 
a volume as possible. 

Since December, 1909, nearly one hundred assays by this method 
have been made by the writer and so far practically no trouble has 
been experienced. Of course, this method is available only where 
the morphine is not combined with other alkaloids, the identity of 
the alkaloid being taken for granted, but as a check on the manu- 
facture of pills, tablets, etc., it has given good results. 

, A comparison of results obtained by the two methods follows. 



10 C.C. OF A 2 PER CENT. SOLUTION MORPHINE SULPHATE. 

By Alcohol-chloroform Method. 

I 0.1984 Gm. morphine sulphate = 99.2 per cent. 

77 0.1976 Gm. morphine sulphate = 98.8 per cent. 

By Phenyl-Ethyl Alcohol and Benzene Method. 

A =0.1827 Gm. = 91.35 per cent. 

B =0.1919 Gm. = 95.95 per cent. 

The solution containing 1 Gm. morphine alkaloid and 50 c.c. 
n/io acid in 100 c.c. gave by direct titration 0.0981 Gm. morphine 
alkaloid in 10 c.c. and by extraction. 

By alcohol-chloroform. By phenyl -ethyl-alcohol & B. mod. 

1 0.09812 Gm. =98.12 per cent \ 

tt n >. * 4. 1 =0.08729 Gm. = 87.29 per cent. 
II 0.09752 Gm. = 97.52 per cent J / y ' * v 

Time required for phenyl-ethyl alcohol method, 4 to 7 hours. 
Time required for alcohol-chloroform method, 2 to 3 hours. 



Analytical Department, Parke, Davis & Co., Detroit, Mich. 



Am. Jour. Pharm. 
July, 1914. 



Bichloride of Mercury Tablets. 



313 



BICHLORIDE OF MERCURY TABLETS AND BICHLORIDE 



In presenting a paper on such a hackneyed subject as " Bichloride 
of Mercury Tablets and Bichloride Tablet Legislation," I am well 
aware that I may be trying your patience on a subject that you may 
perhaps consider as threadbare. My association with and study 
of this subject, however, convince me that this is not a dead subject, 
but contains several problems directly associated with the duties of 
the druggist and which pharmacists themselves, in a very large 
measure, must decide. 

The extensive use of corrosive sublimate in this form has justi- 
fied the decision of the Committee of Revision of the U. S. P. to 
introduce an official formula and by this means to endeavor to 
formulate additional safeguards to life in their use. The articles 
that have appeared in the medical, pharmaceutical and lay press, 
as well as the discussion in the committee, demonstrate that this is 
a live subject, and associated with it are several questions still to be 
settled. 

In the official recognition of the tablet of mercuric chloride the 
U. S. P. is only following the example of most of the pharmacopoeias 
that have been revised in recent years. A study of the foreign 
formulas and a comparison of these and likewise of the commonly 
used American formulas are interesting. 

In American practice, either the Wilson formula containing- a 
mixture of mercuric chloride and ammonium chloride or the Bernay 
formula containing mercuric chloride and citric acid has hem 
almost exclusively used. In Europe the formula proposed by 
Angerer for Pastilla Hydrargyri bichlorati has been the type fol- 
lowed. His formula was : 



TABLET LEGISLATION. 1 



By George M. Beringer. 



Mercury bichloride, 
Sodium chloride, aa 
Eosin 



1.0 Gm. 



0.5 Kg. 



1 Read before the New Jersey Pharmaceutical Association, Lake 
Hopatcong, N. J., June 17, 1914. 



3H 



Bichloride of Mercury Tablets. 



{Am. Jour. Pharm. 
July, 1914. 



Mix the salts and color the mixture with the eosin dissolved in 
water. Allow the mixture to dry in the air and compress into 
portions weighing i or 2 grammes each. 

The German Pharmacopoeia iv (1900), and again in the fifth 
edition (1910), adopts the title " Pastilli Hydrargyri bichlorati " and 
directs that from a mixture of equal parts of mercuric chloride and 
sodium chloride colored with a red coal-tar dye are to be made 
cylinders twice as long as thick and weighing 1 or 2 grammes each. 
Sublimate pastilles must be dispensed in sealed bottles labelled 
" Poison, " and each pastille must be wrapped in black paper on 
which is printed in white the word " Poison " and the content of 
mercuric chloride stated in grammes. 

The Swedish Pharmacopoeia (1901), under the title of Pastilli 
chlorati hydrargyria, directed that " Sublimate pastilles " should be 
hard cylinders or prisms weighing' either 1 or 2 grammes each and 
composed of equal parts of mercuric chloride and sodium chloride 
and colored red by an aniline dye. It likewise introduced the re- 
quirement that each tablet must be wrapped in black paper on 
which was printed in white the word " Poison." 

The Austrian Pharmacopoeia (1906), under the title Pastilli 
hydrargyri bichlorati corrosivi, directed that equal parts of mercuric 
chloride and sodium chloride should be triturated to a thorough 
mixture and colored with a solution of eosin and compressed into 
pastilles weighing 2 grammes or 1 gramme. The pastilles are 
directed to be dispensed in glass bottles under a poison label, and 
the pastilles are to be singly wrapped in black paper with the word 
" Poison " imprinted in white. 

The Swiss Pharmacopoeia (1907) adopts as a title " Hydrargy- 
rum bichloratum compressum," and as synonym " Pastilli Sub- 
limati." The formula is mercuric chloride 666 Gm., sodium chloride 
333 Gm., Eriocyanin A 1 Gm., mixed and compressed into tablets 
weighing 37.5 eg., 75 eg., and 1.5 Gm., and containing respectively 
each 25 eg., 50 eg., and 1 Gm. of corrosive sublimate. It directs 
that each tablet must be wrapped in black paper on which is printed 
in white the weight of the sublimate contained, the word " Poison," 
and a death-head design. 

The British Pharmaceutical Codex, in the first edition of 1907, 
and likewise in the 191 1 edition, gave formulas for a series of these 
tablets. Under the name of " Solvellse Hydrargyri Perchloridi, — 
Soluble Mercuric Chloride Tablets," and as a synonym " Antiseptic 



Am 'ju < iy r 'i9 P i4 arm "} Bichloride of Mercury Tablets. 315 

Perchloride, or Corrosive Sublimate, Tablets," it directed a mixture 
of equal parts of mercuric chloride and sodium chloride colored with 
methyl violet to be compressed into tablets containing 8.75 grains of 
the mercuric chloride, so that one dissolved in the imperial pint 
(20 fl. ozs.) of water will make a 1/10 per cent. (1 in 1000) solution 
of mercuric chloride. Under the title " Solvellse Hydrargyri Per- 
chloridi Fortes or Strong Soluble Mercuric Chloride Tablets," 
a tablet of the same percentage of essential ingredients, but double 
the weight, was directed so that one dissolved in 20 fluidounces of 
water makes 1/5 per cent. (1 in 500) of mercuric chloride. Other 
formulas are given for a " mild " and for a " small " soluble mercuric 
chloride tablet yielding, when dissolved as directed, solutions 1 in 
4000 and 1 in 4500, the latter being especially recommended as suit- 
able for ophthalmic purposes. 

The French Pharmacopoeia (1908) presents a new style of 
formula* for use of mercuric chloride in antiseptic solution. Its 
formula for Papier au Chlorure Mercurique or Charta hydrargyri 
bichlorati directs that 5 Gm. each of mercuric chloride and sodium 
chloride be dissolved in a sufficient quantity of distilled water to 
obtain a volume of 20 c.c. Filter-paper purified by treating with 
water containing one part of hydrochloric acid to the thousand, 
washing with pure water and drying, is then saturated with the 
mercuric chloride solution so that each rectangular surface 5 cm. 
by 10 cm. shall imbibe 1 c.c. of the solution and represent 25 eg. of 
mercuric chloride. The superscription, " Corrosive Sublimate " 
" twenty-five centigrammes," is directed to be printed with indigo 
carmine, thus producing, when immersed in the proper volume of 
water, a blue solution. The paper is to be protected from light 
and moisture and the container to be labelled in indelible red letters 
b POISON." 

These specifications of the Pharmacopee Francaise, official in 
that country since July 17, 1908, will yield a product essentially the 
same as the corrosive sublimate leaflets now being made by an 
American manufacturer who claims originality and the right to a 
patent thereon as a new and novel invention. 

The Italian Pharmacopoeia (1909) gives the title " Pastiglie di 
Cloruro Mercurico " with the latin Pastilli bichlorureti hydrargyri. 
Its formula is mercuric chloride and sodium chloride equal parts 
colored with an aqueous solution of eosin and compressed into cir- 
cular pastilles of 1 or 2 grammes in weight. 



316 Bichloride of Mercury Tablets. {^mSI'jSSl^ 

It is to be noted that most of the foreign pharmacopoeias have 
simply followed in their titles that proposed by Angerer, and desig- 
nate these tablets as pastilles. In the same pharmacopoeias the title 
pastilli is frequently applied to mild remedial agents dispensed in 
the form of confections or lozenges. It is certainly an unfortunate 
designation and a dangerous classification that would include such 
a toxic form along with worm lozenges, cough troches, peppermint 
drops, etc. It is still more to be regretted that it has been proposed 
to adopt this same title in the U. S. P. IX. The use of the word 
" pastille " in this connection is not in accordance with the English 
usage of this word. As defined in the dictionaries the word 
"pastille " refers to several forms of substances of an entirely differ- 
ent character and dissimilar use. 

The Century Dictionary defines pastille or pastil : 
" I — A small roll of aromatic paste, composed of gum benzoin, 
sandalwood, spices, charcoal powder, etc., designed to be burned as 
a fumigator. 

" 2 — A kind of sugared confection, usually of a strong flavor, of 
a round flat shape, like peppermint drops. 

"3 — In art: (a) a thin, round cake of water color; (b) the 
method of painting with water colors prepared as pastils or a draw- 
ing produced by them. 

" 4 — In pyrotechny a paper case filled with a burning composition, 
intended to cause rotation of a wheel." 

Neither of these definitions would cover a mercuric chloride 
tablet of the shape described and the intended use. In medicine 
and pharmacy this title had already been preempted and used to a 
considerable extent for medicated confections, and its adoption for 
such a toxic official preparation is an exceedingly dangerous experi- 
ment. It was probably for this reason that the Pharmacopoeia 
Helvetica adopted as its title " Hydrargyrum bichloratum com- 
pressum," and the British Pharmaceutical Codex " Solvellse." The 
" Solvellse " of the Codex are compressed tablets or discs intended 
to be dissolved in water for external or local use. The attempt at 
classification here made is a step in the right direction. The title 
coined, however, does not indicate the toxic character and, more- 
over, is subject to the criticism that it has the appearance of an 
attempt to imitate the trade-marked name of a certain brand of 
tablets extensively used in England. 

The necessity is for a distinct title that will clearly differentiate 



Am jui° y ur i9i4 arm *} Bichloride of Mercury Tablets. 317 

between the medicinal tablets used so extensively for oral adminis- 
tration and such poisonous tablets intended for external use. The 
safeguarding of life is the first and principal consideration, and this 
warrants the coining of a new title that shall distinguish the latter 
as a separate and distinct class. For this purpose I propose 
Toxitabellce as a distinctive class title, and as the official title for 
these tablets, " Toxitabellse Hydrargyri Chloridi Corrosivi," and as 
the English, " Poison Tablets of Corrosive Mercuric Chloride." 

The foreign formulas follow the formula of Angerer in directing 
equal parts of mercuric chloride and sodium chloride. The Ameri- 
can manufacturers generally claim, on their labels to adhere to the 
Wilson formula. Tablets containing the proportion of ammonium 
chloride directed in this latter formula are prone to change on keep- 
ing. They deliquesce in humid atmospheres, and the solubility also de- 
teriorates with age. For these reasons, some of the manufacturers 
have already substituted sodium chloride for part of the ammonium 
chloride. One manufacturer advises that he has found preferable 
a mixture of corrosive sublimate 7.3 parts, ammonium chloride 2.7 
parts, sodium chloride 5 parts. The entire replacement of the 
ammonium chloride by the sodium chloride will doubtless yield a 
more stable and soluble tablet, and this change should be adopted 
in the pharmacopceial formula. 

The coloring of bichloride of mercury antiseptic tablets was 
originally proposed not only to make them distinct in color from 
other tablets of the same shape and size, but the primal idea was 
to obtain a solution that would have a distinct color and not be 
mistaken and administered for harmless medications or water. Such 
accidents had occurred, and to prevent recurrence Angerer proposed 
as an additional safeguard that the solutions should be colored. It 
has been difficult to select a red dye that would possess sufficient 
tinctorial strength so that only a minute quantity would be required 
and at the same time be permanent and not altered by the action of 
the chemicals nor fade on keeping. This problem has confronted 
the manufacturers and has been the subject of considerable experi- 
mentation on the part of the writer. 

Eosin in the quantity proposed yields a tablet that is distinctly 
pink, but when in solution (1 HgCl 2 in 1000) does not show a dis- 
tinct color. This practical difficulty with the red dyes, their variable 
shades, and, moreover, the fact that confections are frequently of 
this color and liquid medicines are likewise commonly some shade 



318 Bichloride of Mercury Tablets. { Am 'jui°y r *i9 P i4 arm ' 

of red, have led to the use of other colors. The British Pharma- 
ceutical Codex directs methyl violet, which in this combination gives 
a blue-purple solution. The Swiss Pharmacopoeia orders Eriocy- 
anin A, the sodium salt of a sulphonated dye of the triphenyl- 
methane-carbinol type that colors silk and wool a bright blue and 
is only slightly affected by 10 per cent, hydrochloric acid. The 
French Codex directs indigo carmine for this purpose. 

A number of the manufacturers are already giving preference to 
the blue tablets. One of these writes : " Green and red colored 
tablets are not at all satisfactory. I believe that you will agree with 
me that a sombre blue would prove the most desirable. Confections 
are made in red, green, yellow, white, and every conceivable color, 
but the blue is not attractive and therefore would in all probability 
prove the safest. On the question of coloring for mercuric chloride, 
Dr. A. G. Rosengarten, whose firm prepares large quantities of 
mixed salts already colored for the manufacturers, writes me ; 

" The only satisfactory color that we have found is the blue dye, 
called indigo carmine. We have not yet found a satisfactory red or 
green dye, but I can highly recommend indigo carmine for consistent 
results, and a definite weight of that dye added to a definite weight 
of corrosive sublimate mixture will produce definite results. I can- 
not say the same about the other dyes, and I think it will be most 
desirable to confine the dyes for corrosive sublimate mixture to 
the one color, blue, and the one dye, indigo carmine." 

My own experiments confirm these statements as to the avail- 
ability of indigo carmine for this purpose. 2.5 mg. per tablet is ' 
sufficient to color 500 c.c. of water a distinct blue. If a more 
intense color be desired, this can be increased up to 5 mg., and the 
quantity to be specified in the formula for 100 tablets should not 
exceed .5 Gm. In my experiments with red dyes, iod-eosin and 
alizarin carmine (sodium alizarin sulphonate) appear to have given 
the best results with the Wilson type, but the color of the solutions 
is not as bright a red as might be desired. With the Bernay" formula 
containing citric acid, methyl orange has shown the best results. 

The official tablet should be adjusted to the basis of one tablet to 
500 c.c. of water, yielding a 1 in 1000 solution, instead of one tablet 
to the pint, as has been the custom. This will necessitate only a 
slight increase in the weight. 



Am j«u°y r i9i4 arm '} Bichloride of Mercury Tablets. 319 

The shape to be adopted for the official bichloride tablets is one 
of the questions that is being considered. When these tablets were 
introduced, the manufacturers quite naturally used the moulds that 
they had for their compressing machines, and so the unfortunate 
mistake was made of manufacturing these of the round or disc 
shape ; the same shape and sizes as were used for innocuous medi- 
cinal tablets and confections. Fatal accidents have demonstrated 
that it is imperative that this dangerous practice should be discon- 
tinued. Toxic tablets of the bichloride of mercury antiseptic type 
should be made in a distinct shape that has not been used for any 
other purpose, and the use of such a shape or form should be restricted 
by legal enactments* to such toxic tablets intended for external use. 

In recent years the ingenuity of the American manufacturer has 
been exercised to obtain a distinctive shape that should characterize 
and distinguish his brand of " antiseptic tablets." As a result, we 
now have such shapes as triangular, diamond, square, cube, key- 
stone, clover leaf, exploited as proprietary forms of antiseptic 
tablets. Every one of these shapes has been commonly used in 
confections, and their official recognition and continuance for 
bichloride antiseptic medication would be a repetition of the original 
fatal error as to the shape of such tablets. The manufacturers of 
these shapes are each clamoring for the recognition of his par- 
ticular shape. 

The influence of these commercial interests has been exerted to 
prevent legislative action that would designate an appropriate shape 
or judicial consideration that would permit judgment to crystallize 
in favor of an official shape that would insure the greatest amount 
of protection to life. After all, the question of safety first is the 
paramount question. 

Of all the proposals for a shape for bichloride of mercury tablets, 
the coffin shape suggested by Mr. F. M. Apple in his paper before 
the Pennsylvania Pharmaceutical Association seems to be best. This 
has already been adopted by at least four manufacturers, and its 
general adoption has only been prevented by the commercial in- 
terests back of other designs. Commercial instincts and financial 
advantages, and not the broad humanitarian principle of what is 
best to protect life, have been the causes actuating the opposition to 
legislation and to official recognition of the best suggestion yet 
offered. 

The German Pharmacopoeia has been quoted as an authority 



320 Bichloride of Mercury Tablets. { Am - ^Jj™- 

to be followed in fixing the U. S. P. standard. I believe that we 
should appropriate from the foreign pharmacopoeias all that our 
experience and judgment prove to be correct and in accordance with 
American practice. In this instance I cannot approve of following 
the dictum of the German Pharmacopoeia. I have here a sample 
of the official German corrosive sublimate tablets that have been in 
my possession since last March. You will observe, first, that these 
are not uniform in color and that fading has commenced to take 
place. Secondly, the shape is in conformity with that of the Ph. Gr., 
twice as long as broad, and the manufacturer, to show this and 
possibly to permit of economy in using only half a tablet at a time, 
has made them with a ridge across the centre. This resembles forms 
of the pink linked phenolphthalein and other proprietary laxative 
wafers that are so extensively used in this country. It would be 
difficult to conceive of a more dangerous experiment than to officially 
recognize such a shape for bichloride tablets. It would be on a par 
with the adoption of the Italian pharmacopceial standard of the 
round tablet which we are now ready to condemn. There is no 
uniformity in the European pharmacopoeias on this formula, and 
so the argument for adopting an international standard falls flat. 
Thirdly, the solution, when made of a strength of I to iooo, as 
commonly used, is so delicate a pink tint as to be barely perceptible. 

So far as I know, no American manufacturer has yet placed on 
the market a bichloride of mercury tablet copied after that of the 
German Pharmacopoeia. As this formula has been published for 
more than fourteen years, this is noteworthy and may be construed 
as an evidence of the good judgment of our manufacturers. To 
now insist that the U. S. Pharmacopoeia must adopt and make legal 
a shape that has not met favor in American practice is a unique 
proposition that lacks the popular approval that is essential to its 
effectiveness. 

The importance of throwing every safeguard possible around the 
sale and handling of such poisonous substances is now thoroughly 
recognized. The newspapers have given wide publicity to the 
deaths, either suicidal or accidental, occurring from bichloride 
tablets. The evils resulting from the overzealous newspaper which 
gives its readers all the details of the method by which some poor 
unfortunate has gone on the long voyage, have been discussed and 
decried, yet, nevertheless, it continues its course with little or no 
abatement. 



Am j.u°y r i9i4. ann " } Bichloride of Mercury Tablets. 321 

A number of State legislatures in session during the past year 
have had under consideration acts that would restrict the handling 
of such poison tablets and define their shape, color, and label, and 
further prohibit the use of the prescribed shape for any other 
purpose. There are at least three bills on the same subject now 
pending in Congress. It is certain that we may expect legislation 
before long on this entire matter, and it is eminently proper that 
the drug trade should take an active interest in solving a question 
of public safety that is so closely associated with our business. Un- 
fortunately, the attitude assumed by some of the druggists is that 
of thoughtless indifference. The argument advanced by others is 
that such legislation is only a passing sentimental fad and that it can 
have no influence on the protection of life. This is so fallacious that 
it can not long continue to prevent legislation. 

It was never expected that any legislation would prevent a person 
of morbid mind from committing suicide. This is not the purpose 
of the proposed legislative enactments, but it is contended that in 
prescribing a distinctive shape for these poison tablets they could 
under no circumstances be mistaken, either in the day or night, for 
harmless medications. If a distinctive shape had been supplied the 
Macon, Ga., banker and the Brooklyn business man, whose deaths 
beyond question were accidental poisonings, at least these lives could 
have been spared. 

The necessity for a distinctive shape for bichloride of mercury 
tablets is well shown by the compilation appearing in Public Health 
Report No. 46, by Martin I. Wilbert, of the United States Public 
Health Service. In this compilation Mr. Wilbert shows that at 
that time, in the current price-lists of five leading pharmaceutical 
manufacturers, there were sixteen different formulas and varying 
sizes of poison bichloride tablets, five different shapes, five different 
colors, and only three out of the sixteen were then made of any 
other shape than the ordinary round tablets used for medicine, such 
as headache and cold tablets. Could any stronger evidence of the 
necessity for restrictive legislation and a distinctive shape for these 
poison tablets be presented than this compilation in a Government 
bulletin, which shows the present dangerous and unsatisfactory 
method of marketing these tablets ? 

The influence of certain manufacturers on proposed legislation is 
shown in the act passed by the last session of the Maryland legis- 
lature. Instead of specifying in the act a distinctive shape or color, 



322 



Liquid Petrolatum. 



Am. Jour. Pharm. 
July, 1914. 



the value of the legislation is largely nullified by the amended form 
in which the bill was passed. This law provides that " Tablets con- 
taining more than i/io grain of mercury bichloride must be of 
either triangular, diamond, square, oblong, or other irregular shape, 
and their color must be either blue, purple, or green, with the word 
' Poison ' imprinted or embossed on each tablet. Further, these 
tablets can only be sold, dispensed, or given away in bottles upon one 
side of which the word ' Poison ' has been blown, and when a label 
with the word ' Poison ' is placed on the face of the bottle." 

The restrictions regarding the package and labelling are such as 
are commonly employed by all of the manufacturers, but the very 
needed protection to the consumer has been lost sight of by the over- 
powering commercial spirit that prevented the selection of a dis- 
tinctive shape for the tablets. Any one of a number of shapes is 
equivalent to no shape, and the very indefiniteness of the act as 
passed through the influence of the manufacturers destroys its value 
as a measure for the safety of the public. 



LIQUID PETROLATUM OR " RUSSIAN MINERAL OIL." 

Report of the Council on Pharmacy and Chemistry. 

The following report was submitted to the Council by a referee 
and publication authorized. 

W. A. Puckner, Secretary. 

Petroleum has been in use as a medicine from time immemorial. 
It was known to Herodotus 400 years before Christ, and is mentioned 
by Plutarch, Dioscorides, Pliny, and other early writers. It was 
extensively used by the Arabians and evidently played an important 
part in the practice of medicine in India, being known to the Benga- 
lese as Muthe Katel. The raw product was the substance used in 
earlier times and differed much in character and composition, as 
obtained from different sources. 

As an internal remedy it was early employed in chronic 
pulmonary affections, in obstinate skin diseases, in rheumatism, and 
for the expelling of tapeworms. It was extensively used for these 
several purposes in France under the name " Oleum Gabianum " and 
in North America as " Seneka oil." The internal use of the refined 
product may be traced to a patent granted to Robert A. Chesebrough, 



^Jufy, r i9u arm '} Liquid Petrolatum, 323 

of New York, in June, 1872, for the manufacture of a " new and 
useful product from petroleum, named vaseline." This name was 
originally applied only to a semisolid preparation, but later a liquid 
product known as liquid vaseline was marketed and for a time ex- 
ploited as a cure for coughs, colds, consumption, and a number of 
other diseases and conditions. 

The liquid petrolatum has since become known under a variety 
of names, proprietary and otherwise, in addition to being used as a 
substitute or an adulterant for other, more costly, fats and oils. 
Some of the names applied to the product are : 



Adepsine oil 


Neutralol 


Amilee 


Olo 


Atoleine 


Paraffin oil 


Atolin 


Paroline 


Blandine 


Petro 


Crysmalin 


Petrolax 


Deeline 


Petrolia 


Glyco 


Petrolol 


Glycoline 


Petronol 


Glymol 


Petrosio 


Heavy petroleum oil 


Rock oil 


Liquid albolene 


Russian liquid petrolatum 


Liquid cosmoline 


Russian mineral oil 


Liquid fossiline 


Russian paraffin oil 


Liquid geoline 


Russol 


Liquid paraffin 


Saxol 


Liquid petrolatum 


Terralbolia 


Liquid saxoline 


Terraline 


Liquid vaseline 


Usoline 


Mineral glycerin 


Water-white mineral oil 


Mineral oil 


White paraffin oil 



A preparation similar to that official in the Pharmacopoeia of 
the United States as liquid petrolatum has been included in many, 
if not all, of the foreign pharmacopoeias, the official title under which 
this preparation is recognized being as follows : 

Petrolatum liquidum, U. S. Pharmacopoeia ; Paraffinum liquidum, 
pharmacopoeias of Great Britain, Germany, the Netherlands, Japan, 
Belgium, Austria, Denmark, Switzerland, Sweden, Servia, Italy, 
Hungary and Russia ; Oleum Paraffinse, Spanish Pharmacopoeia ; 
Vaselinum liquidum, French Pharmacopoeia, and Oleum vaselini 
(as a synonym), pharmacopoeias of Denmark and Russia. 



324 



Liquid Petrolatum. 



I Am. Jour. Pharm. 
I July, 1914. 



The requirements of the several pharmacopoeias differ somewhat, 
and the specific gravity as given is as follows : 



For pharmaceutical purposes, liquid petrolatum may be divided 
into two grades, the lighter or more limpid oil, used extensively as a 
vehicle for oil sprays, and the heavier, more viscid oil generally 
recognized in European pharmacopoeias and used as an ingredient 
of ointments and more recently as a remedy in the treatment of 
intestinal stasis. 

Under petrolatum liquidum the U. S. P. recognizes a mixture of 
hydrocarbons, chiefly of the methane series, which occurs as a color- 
less or very slightly yellowish, oily, transparent liquid without odor or 
taste and having a specific gravity of about 0.870 to 0.940 at 25 C. 
For the U. S. P. IX, it is proposed to change this requirement some- 
what so as to have it apply to a transparent liquid free from fluores- 
cence, without odor or taste and having a specific gravity of from 
0.845 to °-94P at 25 C. 

Such a requirement would include all of the available paraffin 
oils, irrespective of origin. The now commonly available commercial 
liquid petrolatum, used for pharmaceutical purposes, is practically 
colorless and all of the better grades are free from odor or taste. 
The specific gravity varies from 0.855 to 0.895. The lighter oils, 
having a specific gravity of from 0.860 to 0.870, are usually preferred 
in the making of oil sprays or solutions of substances to be used as 



U. S. P. VIII, 1905 

Ph. Brit. IV, 1895 

B. P. C. II, 191 1, usually 

Ph. Germ. V, 1910, at least . . 

Ph. Ross, VI, 1910 

Ph. Hung. Ill, 1909 

Ph. Ital. Ill, 1909 

Ph. Fr. V, 1908, about 

Ph. Serb. II, 1908, about 

Ph. Svec. IX, 1908 

Ph. Helv. IV, 1907 

Ph. Dan. VII, 1907, at least . . 
Ph. Austr. VIII, 1906, at least 
Ph. Belg. Ill, 1906, not below . 

Ph. Japon. Ill, 1906 

Ph. Ndl. IV, 1905, not below 
Ph. Hisp. VII, 1905 



0.870 to 0.940 at 25 
0.885 to 0.890 at 1 5. 5 
0.875 or lower at 15 
0.885 at 15° 

0.880 to 0.885 at 15° 
0.88 to 0.89 at 1 5 
0.875 to 0.890 at 15 
0.875 at 15 

0.880 at 15° 

0.88 to 0.90 at 15 
0.880 to 0.885 at 15° 
0.880 at 15° 

0.880 at 15° 

0.880 at 1 5° 

0.875 to 0.945 at 15 
0.860 at 1 5° 

0.840 at 15 



Am. Jour. Pharm. 
July, 1914. 



Liquid Petrolatum. 



325 



local applications. The product having" a specific gravity above 
0.875 evidently contains a considerable amount of dissolved solid 
paraffin which separates out at temperatures at or below o° C, but 
readily dissolves again at temperatures above io° C. 

There is considerable difference in the chemical composition of 
the paraffin oils obtained from various sources. The American oil 
consists largely of hydrocarbons of the methane series, while the 
Russian oil contains naphthenes or hydrocarbons of the benzene 
series, having the empirical composition of ethylene (CnH 2 n), which 
may be considered as hydrogenated aromatic hydrocarbons, though 
they behave with reagents very much in the same way as do the 
hydrocarbons of the methane series. 

Mineral oils with a naphthene base are best suited for making 
white petrolatum, and at the present time the production of the 
colorless water-white liquid petrolatum appears to be confined largely 
or almost exclusively to the crude product of the Baku district of 
Russia, though it is asserted that it is now also made from the 
Hanover (Germany) crude oil and that some is being produced by 
" cracking " the white solid paraffin. 

It is also said that the American oil can be made water white, but 
that it is not being so produced at present for economic reasons ; the 
yellowish oil, free from fluorescence, having a very wide sale, both 
as a lubricant and as a substitute for lard oil and other of the more 
costly lubricating oils. 

From a pharmaceutical point of view it would appear important 
to note the physical characteristics of the oil and to insist on absence 
of color, absence of odor and taste, absence of acid and of alkali 
and a specific gravity in harmony with the purposes for which the 
oil is to be used. 

During the past year or two liquid petrolatum has attracted 
considerable attention as a remedy in the treatment of intestinal 
stasis or chronic constipation, the practice of using it having been 
developed largely through its recommendation by Sir W. Arbuthnot 
Lane and his associates. This use of liquid petrolatum and of 
petrolatum products generally is by no means novel. N. A. 
Randolph, 1 of Philadelphia, was among the first to suggest its use 
for this purpose in an article published in 1885. Randolph also ap- 



1 Randolph, N. A. : Therap. Gas., 1885, ix, 732. 



326 



Liquid Petrolatum. 



( Am. Jour. Pharm. 
\ July, 1914. 



pears to have been the first to experiment with petrolatum and to 
determine its non-absorbability from the intestinal tract. In an 
article 2 in 1884 he concludes that " pure petrolatum while entirely 
unirritating to the digestive tract is valueless as a foodstuff." 

The experiments recorded by Randolph were evidently prompted 
by the fact that vaseline and a number of imitation products then on 
the market were being sold as substitutes for lard and butter, and 
opinions regarding the food value of petroleum products appear to 
have differed very materially. Following the experiments of 
Randolph, Robert Hutchison in 1899 ma de a series of experiments 
to demonstrate that petroleum, petrolatum, paraffin and related prod- 
ucts were absolutely unassailable by any of the digestive fluids, 
despite the "large vogue that had of late years been given to various 
petroleum emulsions, chiefly by ingenious and unterrified advertis- 
ing." He came to practically the same conclusions arrived at by 
Randolph fifteen years earlier and pointed out that " liquid paraffin 
in one sense may be regarded as an artificial intestinal mucus and 
might in that way have some value on certain forms of constipation." 

William Dufifield Robinson 3 reports on the use of a perfectly 
refined colorless and odorless petrolatum, supposedly of American 
origin. He was able to show that all of the product passed un- 
changed through the intestinal tract and could be regained from the 
faeces. In his conclusions he expressed the belief that the effect 
of the administration of these petroleum products is far more than 
as a simple intestinal lubricant. In over fifty selected cases in which 
nutrition, digestion and body-weight were impaired, and the purest 
oil administered in 1- or 2-dram doses each day for a period of 
from four to six months, there was in every instance an improvement 
of weight, health and feeling of well-being. The administration 
of refined paraffin oil gave no discomfort in any instance, even in 
cases in which nearly a pint was given in a few hours. 

William Ewart 4 suggests liquid paraffin as a safe agent for the 
local treatment of the lesions in typhoid fever. He says in part: 
" Mineral oil, such as petrolatum or paraffin, is neither absorbed 
nor dissolved ; therefore, after all absorbable ingestions are taken 
up by the lacteals, it will still remain in the bowel. In this way pure 



2 Randolph, N. A.: Proc. Acad. Nat. Sc., Philadelphia, 1884, p. 281. 

3 Robinson : William Duffield : Med. News, 1900, lxxvii, 56. 

4 Ewart, William : Brit. Med. Jour., 1902, ii, 1505. 



Am 'jui7 r i«Ji4 arm ' } Liquid Petrolatum. 327 

liquid paraffin is valuable, precisely because it is inert ; moreover, 
it might some day, perhaps, be made the vehicle for effective topical 
remedies." 

A. D. Schmidt 5 quotes Stubenrath as having given liquid paraffin 
in the treatment of chronic constipation, and he himself gave as 
much as 20 gm, of liquid paraffin to adults without observing any 
injurious effect whatever. He says, " As a result of the administra- 
tion of liquid paraffin, the faeces are softened considerably and are 
found under the microscope to contain numerous minute globules 
of paraffin." He was, however, unable to recover from the faeces 
the entire quantity of paraffin administered and believes that a 
certain portion of it, probably the fractions with a low boiling-point, 
are absorbed or possibly oxidized in the organism. 

Maurice Vejux Tyrode also refers to the use of liquid petroleum 
in the treatment of constipation. 

Sir F. Arbuthnot Lane in his recommendations of liquid petrola- 
tum calls it an ideal remedy for stasis, but cautions against the use 
of the lighter oil as extensively prescribed in this country as a 
vehicle for sprays in nose and throat work. 

Paraffin oil is not absorbed from the alimentary tract and so far 
as known exerts no deleterious influence. It is usually given in 
quantities of from 10 to 20 c.c. half an hour or an hour before meals 
or in larger doses, from 30 to 50 c.c, at one time on retiring. From 
available evidence it appears that comparatively huge doses may be 
administered without the production of any untoward results. Ac- 
cording to many observers, liquid paraffin should not be given with 
or after meals because of the inhibiting influence that it may have 
on the digestion of food. It is not soluble in water or the ordinary 
solvents and therefore cannot be diluted. The denser oils are pref- 
erably slightly warmed or drunk with warm water so as to obviate 
the disagreeable slimy sensation that persists when taken cold. 

Volatile oils may be used in moderate amounts to give a dis- 
tinctive taste to the otherwise rather insipidly tasteless paraffin oil. 
Among the more desirable oils to be used for this purpose would be 
oil of nepne r mint, oil of cinnamon, oil of betula or methyl salicylate 
and oil of cloves. From 2 to 10 drops of any of these oils can be 
added to a pint of the oil. When larger doses of the oil are to be 



5 Schmidt, A. D. : Milnchcn. mcd. Wchnschr., 1005, Hi, T907. 

8 Tyrode, Maurice Vejux: Boston Mcd. and Surg, Jour., 1010, clxii, 673, 



328 



Liquid Petrolatum. 



J Am. Jour. Pharm. 
\ July, 1914. 



given at one time, it would, of course, be advisable to use a com- 
paratively smaller quantity of the volatile oil as a flavor. 7 

From the foregoing it would appear that apart from the 
Pharmacopoeia of the United States, practically all other known 
pharmacopoeias describe a water-white mineral oil under the title 
" Paraffinum Liquidum " or " Liquid Paraffin " as a colorless, odor- 
less, tasteless, non-fluorescent, oily liquid, free from acids, alkalies 
and organic impurities. As explained before, the specific gravity of 
the preparation as recognized in other countries and as offered on 
the American market at the present time varies considerably, and 
there appears to be some difference of opinion as to the exact nature 
of the product that is preferable for use for different purposes. 
This matter requires further investigation. 

Since the definition of liquid petrolatum in the U. 9. Pharma- 
copoeia permits the use of fluorescent products of widely varying 
specific gravities, it is recommended that physicians who desire the 
water-white non-fluorescent (Russian) mineral oil should use the 
term " Petrolatum Liquidum, Grave," or " Paraffinum Liquidum, B. 
P.," if the heavy product recommended by Lane is desired, and " Pet- 
rolatum Liquidum, Leve," if the light varieties are required. It is 
further recommended that under the foregoing names manufacturers 
and pharmacists be requested to dispense the products, in accord- 
ance with the following descriptions : 

Petrolatum Liquidum, Grave. — Heavy (Russian) Liquid Pet- 
rolatum. — Paraffinum Liquidum, B. P., liquid paraffin. — A trans- 
parent, colorless, tasteless, non-fluorescent, oily liquid, odorless when 
cold but giving off a faint petroleum odor on heating. This prepara- 

7 In addition to the articles referred to in the preceding footnotes, the 
following are of interest in connection with this subject: 
Editorial, Therap. Gaz:, 1885, ix, 353. 
Junker, F. A.: Med. Record, London, 1885, xiii, 506. 
Editorial, Med. News, 1886, xlviii, 105. 
Dunbar : Deutsch. med. Wchnschr., 1896, xxii, 33. 

Stubenrath, Franz Casimir : Munchen. med. Wchnschr., 1897, xliv, 639. 

London Letter, Med. News, 1899, lxxiv, 504. 

Hutchison, Robert : Brit. Med. lour., 1899, i, 724. 

Schlesinger, E. G. : Boston Med. and Surg. lour., 1913, clxix, 14. 

Lane, W. Arbuthnot : Brit. Med. Jour., 1913, ii, 1126; Proc. Roy. Soc. 
Med., 1913, vi, 49; Surg., Gynec. and Obst, 1913, xvi, No. 6. 

Jordan, Alfred C. : Practitioner, London, February, 1913. 

Chrysospathes, J. G. : Zentralbl. f. Chir., 1913, No. 45 ; abstr., The Jour- 
nal A. M. A., Dec. 13, 1913, p. 2201. 



Am "j^y^i9i4 arm '} Philadelphia College of Pharmacy. 329 

tion should correspond to the requirements of the British Pharma- 
copoeia for liquid paraffin and have a specific gravity of about 0.885 
to 0.890 at 15 C. It is insoluble in water or alcohol, but soluble in 
boiling absolute alcohol and readily soluble in ether, choloroform, 
carbon disulphide, petroleum benzin, benzene, and fixed and vola- 
tile oils. It serves as a solvent for volatile oils and related sub- 
stances like camphor, menthol and thymol. 

This is the type of preparation used by Sir W. Arbuthnot Lane, 
and his associates for internal administration. It is also used as a. 
basis for ointments and salves and as a local application to wounds, 
ulcers and in certain forms of skin diseases in which a simple pro- 
tective is desired. 

Petrolatum Liquidum, Leve. — Light (Russian) Liquid Petro- 
latum. — A transparent, colorless, tasteless, non-fluorescent, oily 
liquid, odorless when cold, but giving off a faint petroleum odor on 
heating. In other respects this preparation should correspond to 
the pharmacopoeial tests for liquid petrolatum and have a specific 
gravity of about 0.860 to 0.875 at I 5° C. Like the heavy variety 
of liquid petrolatum, it is insoluble in water and alcohol, but soluble 
in boiling absolute alcohol and readily soluble in ether, chloroform, 
carbon disulphide, petroleum benzin, benzene and fixed and volatile 
oils. It serves as a solvent for volatile oils and related substances 
like camphor, menthol and thymol. 

This is a type of preparation extensively used as a vehicle for 
the oily sprays in nose and throat work. It is also being used as one 
of the constituents in the now popular paraffin oil cold cream and 
has been used to some extent for internal administration in the 
treatment of chronic stasis. Being more limpid than the preparation 
preferred by Lane, it is more readily taken, though greater care must 
be exercised in securing a sample devoid of the lighter fractions of 
petroleum distillates. 



PHILADELPHIA COLLEGE OF PHARMACY. 

NINETY-THIRD ANNUAL COMMENCEMENT. 

The commencement exercises on Thursday, June 18th, brought 
to a close one of the most successful commencement weeks in the 
history of the Philadelphia College of Pharmacy. A very large 
number of the alumni visited the college and attended the various 
functions. The Baccalaureate services were held at the Church of 



33o 



Philadelphia College of Pharmacy, j 



Am. Jour. Pnarm. 
July, 1914. 



St. Luke and the Epiphany, the Rev. David M. Steele delivering 
an unusually inspiring sermon. On Monday evening the Faculty 
gave their annual banquet to the graduating class in the College 
Auditorium. This is always a very interesting occasion, in that it 
brings together the Faculty and members of the graduating class in 
a very close relation, enabling them to discuss not only their 
experiences but some of the larger questions of life. 

Tuesday was Alumni Day, the Association holding its annual 
meeting in the afternoon, and in the evening giving a reception to 
the members of the graduating class, in addition to the awards of 
the alumni prizes and a very excellent musical program. Prof. 
Henry Kraemer gave an address, in which he read the class oration 
which he had delivered twenty-five years ago, at the time of his 
graduation from this College. The annual alumni banquet, which 
was held at the Hotel Walton on Wednesday evening, was very 
largely attended and was characterized by magnificent alumni and 
college spirit. The responses by the various representatives of the 
classes ending in 4's and 9's showed that the movement to mark 
the centennial of the College and raise $500,000 for new site, new 
buildings, and additional equipment would receive the hearty 
cooperation of the alumni. 

The commencement on Thursday evening at the Academy of 
Music marked the climax of the week's celebration. The fea- 
ture of the evening was the presence of the Governor of Penn- 
sylvania, Hon. John K. Tener, who delivered a brief but very 
appropriate address'to the members of the graduating class and their 
friends assembled. The opening prayer was made by Rev. W. Quay 
Rosselle, of Philadelphia, after which the degrees were conferred 
by President Howard B. French. 

The title of Master in Pharmacy (Ph.M.) — In Course — was con- 
ferred on Professor Edwin L. Newcomb, P.D., of the University of 
Minnesota. 

The following are the names of those receiving the degree of 
Doctor in Pharmacy (P.D), together with the subjects of their 
graduating theses : 



Name 



Thesis 



Ankrum, Samuel Martin. 

Balliet, Woods D 

Berryman, Clarence Haco 



Acetone 

Serums and Vaccines 

The Presence of Arsenic in Tin 
Foil 



Pennsylvania 
Pennsylvania 



New Jersey 



Am 'juTy!"'i9i4 arm "} Philadelphia College of Pharmacy. 331 

Name Thesis 
Biren, Samuel Show Card Writing, Advertising 

and Displaying Austria 

Botdorf, Joseph Franklin . . . .Kaolinum Pennsylvania 

Boyd, William Merton Improved Methods of Preparing 

some U. S. P. and N. F. 

Preparations Pennsylvania 

Burke, John Joseph Cork: Its Origin and Use New Jersey 

Cahan, Samuel Sapo Mollis Russia 

Cameron, Ernest Clifford .... Production of Cacao Pennsylvania 

Cantner, Paul Clifford Acidum Hydriodicum Dilutum .. Pennsylvania 

Carr, Edmund Eugene Petroselini Fructus Utah 

Coble, Paul Daniel Ammonium Hypophosphite Pennsylvania 

Cohen, Louis Pharmacy in Ireland Pennsylvania 

Collins, John Edmund Sapo Mollis ex Oleo Gossypii 

Seminis Pennsylvania 

Comber, Gertrude Agnes [P.C.] Magnesium Oxide ..Pennsylvania 

Coolbaugh, Leonard Ellsworth Cudbear New York 

Craft, William Wheeler The Typho-Bacterins District of 

Columbia 

Davidson, Wilmer Paul Tincture of Iodine Pennsylvania 

Dickson, Thomas Young Ground Flaxseed Pennsylvania 

Dils, Chauncey Lloyd Manufacture of Window Glass. . Pennsylvania 

Dougherty, Christ Patrick, Jr. Aromatic Spirit of Ammonia. ... Pennsylvania 

Duvoisin, Agnes, [P.C.] Plasters and their Spreading. ... Pennsylvania 

Edwards, Harold Powell Elixir Ferri, Quininse et Strych- 

ninse Phosphatum Maine 

Eldredge, William Payson Phenolsulphonaphthalein : Func- 
tional Test — Pennsylvania 

Epstein, Meyer Charles Chocolate and Cocoa Pennsylvania 

Fiscel, John Arthur Sapo Mollis Pennsylvania 

Fitzsimmons, William Henry. .Crude Petroleum Pennsylvania 

Flanagan, Clark Harrison Compound Syrup of Hypophos- 

phites, U. S. P New York 

Fox, James Andrew Specifications for Portland Ce- 

j ment Pennsylvania 

Frank, William Reuben Incandescent Gas Lighting Pennsylvania 

Fry, Daniel Joshua, Jr Studies of the Origin and 1 ests 

of the True Oregon Balsam. .. Oregon 

Gantert, Charles Louis Mesquite Gum Pennsylvania 

Gehrung, John Clucas An Accounting System for the 

Average-Sized Drug Store. ... Ohio 

Gonya, Harry Herome Calamine Maine 

Gray, John Calvin Gentian Pennsylvania 

Greene, Barnett Russell Hydrogen Peroxide, Production 

Past and Present Pennsylvania 

Griffin, William Harold Theatrical Cold Cream New York 

Hagenman, Joseph Jeremiah. .Diluted Acetic Acid Pennsylvania 



332 Philadelphia College of Pharmacy. { Am - J J u 1 y"'Ji h 4 arm ' 

Name - Thesis 

Hall, Jasper Bonsall Liquor Cresolis Compositus Maryland 

Harris, George Herbert Paregoric Pennsylvania 

Hayes, John Harry Modern Industrial Reducing 

Agents New York 

Heckenberger, William 

Welcome The Three Cinnamons Pennsylvania 

Held, Ray Charles Accurate Weighing Pennsylvania 

Helwig, George L Solution of Magnesium Citrate. . Pennsylvania 

Hinman, Ralph Heber Glycerophosphates '....Pennsylvania 

Hurley, William James Syrup of Quinine Pennsylvania 

Johnson, Clarence Paul Analysis of Viburnum Opulus. .. Illinois 

Johnson, Ernest Irvin Medication of Zinc Stearate Maryland 

Kahler, Frank Lot Eucalyptus Pennsylvania 

Kauffman, Walter Melvin Structure of Viburnum Opulus 

and Various Viburnum Barks . Pennsylvania 

Kentch, Mortimer Adrian Medicated Baths and their Ex- 

) temporaneous Preparation by 

the Pharmacist Pennsylvania 

Kinbach, Edwin Homer [P.C] Glass Graduates Pennsylvania 

Kostenbauder, George Henry. The Extemporaneous Preparation 

of Medical Bougies Pennsylvania 

Krick, Harry Nunemacker. . . .Elixir Terpini Hydratis ...... .". .Pennsylvania 

Kulp, Jacob Harold The Evils of Newspaper Prescrib- 
ing Pennsylvania 

LaCourse, Anthony, Jr Silicon Carbide New York 

La Wall, Edgar Seiple Carbon Dioxide in Atmospheric 

Air and Its Estimation Pennsylvania 

Leidich, Stewart Grier t The Cultivation and Handling of 

Golden Seal Pennsylvania 

Leinbach, Allen Abraham Purity of Commercial Gelatin. .. Pennsylvania 

Llewellin, Walter Palmer Bermuda Arrowroot Bermuda 

Lodge, Roy Paul The Electrolytic Manufacture of 

Organic Compounds and Fine 

Chemicals New Jersey 

McCall, Enzer Lewis Clay Pennsylvania 

McKean, Harold Andrew [P.C] The Salt Industry in New York 

State New York 

McLarren, Chester Lee Piscidia Erythrina Pennsylvania 

Marshall, Forrest Scott Tea and Its Caffeine Yield Pennsylvania 

Merz, Elmer Frank The Phosphates of Calcium Pennsylvania 

Morehead, Robert Crosier. .. .Burgundy Pitch Virginia 

Murtoff, Robert Goulden Acetylene Pennsylvania 

Myers, Nervin Amos Bacterins Pennsylvania 

O'Hare, Charles Vincent Oleum Amygdalae Amarse et 

Benzaldehydum Kentucky 

Owings, Irl Washington Tablet Making in the Retail Drug 

Store Ohio 



Am ' j^°]y r * i9i4 arm ' } Philadelphia College of Pharmacy. 333 

Name Thesis 

Pettit, Roland Levi Face Creams New Jersey 

Rachmell, Nathan Cottonseed Pennsylvania 

Rogers, Ralph Benjamin Acacia New Jersey 

Rosenberg, Julius Jacob Cork New York 

Rosoff, Maurice Drug Standardization and Its 

Value in Pharmaceutical Prep- 
arations Pennsylvania 

Rowland, Norris Dean Colorimetric Test for Cubeb Pennsylvania 

Russell, Charles Allen Potassa Sulphurata Pennsylvania 

Salsbury, Venola Bruce Emulsion of Cod Liver Oil Pennsylvania 

Schadt, Ralph Monroe Insecticides Pennsylvania 

Semmel, Irvin Clarence Prescription Precipitation Pennsylvania 

Shover, Raymond Leslie Assay of Donovan's Solution. ... Pennsylvania 

Shumaker, Henry Ward Hygienic Laboratory of the U. S. 

P. H. Service Pennsylvania 

Slipakoff, Isadore Sponges Pennsylvania 

Spangler, Edwin Royer The Rhizome of Asarum Cana- 

dense Pennsylvania 

Steever, Ernest Leo Maple Sap, Syrup and Sugar Pennsylvania 

Stines, George Findley Carum Ohio 

Sutton, Stanley Eugene Colloids, their Chemistry and 

their Practical and Thera- 
peutical Applications New Jersey 

Taylor, Leander Gifford, Jr. ..Physiologic Saline Solution New Jersey 

Taylor, William Henry Logwood Pennsylvania 

Thompson, Frank Davenport. . Peroxides and Perborates Pennsylvania 

Train, Earl Fred Manna New York 

Trambley, Leo Thomas The Chemistry of Paper Making. Pennsylvania 

Veigel, Charles Joseph Volumetric Estimation of Mer- 
cury Pennsylvania 

Waker, James Schuteman Aromatic Fluidextract of Cas- 

cara New Jersey 

Watson, John Russell Camphor: Natural and Synthetic Pennsylvania 

Watson, Walter Irving Urinalysis Rhode Island 

Way, John Cloud, Jr The Contributions of Ancient 

Greece to Modern Medicine. .. Pennsylvania 

Weinstein. Abram Hirudo Pennsylvania 

Wheeler, Elwyn J Certified Food Colors N.Hampshire 

Whipple, Oscar Kellog, Jr.,. . .Weeds Used in Official Pharmacy New Jersey 
White, Charles Albert, Jr., 

[P-C] Bee Culture and Its Products 

Used in Pharmacy New Jersey 

Willmers, Horace William Sandalwood Iowa 

Wolverton, Fred Cleveland ... Podophyllum : Fruit and Its Ad- 
juvant Syrup Ohio 

Wyman, Abraham Sodium Chloride Pennsylvania 



334 Philadelphia College of Pharmacy. { Am j^ 19 u &rm - 

The following are the names of those graduates who received 
the degree of Pharmaceutical Chemist [P.C.], together with the 
subjects of their theses: 

Name Thesis 
Flack, George Thomas Unfermented Grape Juice, Manu- 
facture and Use Pennsylvania 

Flottman, Charles August Monazite Sand Pennsylvania 

Hansell, Henry Lewis Compound Syrup of Hypophos- 

phites (Cloudy) Pennsylvania 

Heinle, Charles Jacob Paper Pennsylvania 

Hogstad, Anton, Jr Belladonna Wisconsin 

Kutteroff, Charles Frederick. . Camphor and Its Preparations ...New Jersey 
Porter, Clarence Frank Turner Methods for Recovering Volatile 

and Fixed Oils from Emulsions Tennessee 
Quin, John Frederick Gartner. The Production of Cottonseed 

Oil Pennsylvania 

Schoonover, Harold Nelson. .. Buttermilk Cold Cream Pennsylvania 

Wallace, William Romine The Constituents and Manufac- 
ture of Fertilizers Pennsylvania 

Webb, Alvin Chester Galke ex Rhus glabra New Jersey 

Certificates of Proficiency in Chemistry were awarded the 
following : 

Bush, John Lyol Pennsylvania 

Cowles, Henry Carleton, Jr Pennsylvania 

Hinski, Herman Leo [P.D.] Pennsylvania 

Karns, Harry Clifford, Jr. [P.D.] Pennsylvania 

Kind, Paul Adolph New Jersey 

Tucker, George W Pennsylvania 

Certificate of Proficiency in the Food and Drug Course: 
Clark, Roy Lavender Utah 

Certificates in Bacteriology were awarded the following: 

Aguizy, Ahmed Mahmoud El Egypt 

Atkins, John Walter [P.D.] Pennsylvania 

Brown, West Smith [P.D.] Pennsylvania 

Garrett, Joseph Jeffreys Florida 

Hite, Earle Milton Pennsylvania 

Huber, Donald Witherow [P.D.] Pennsylvania 

King, James David [P.D.] Pennsylvania 

Kulp, Jacob Harold Pennsylvania 

Grauss, Gustave Adolph, Jr New York 

Leathers, Fred. S New York 

Lemon, Allan Michigan 

Loehle, Frank Aloysius New York 



Am 'ju! ) y 1 r "i9i4 arm '} Philadelphia College of Pharmacy. 335 

Linford, Louis George New York 

Merrier, Paul Marcus Pfeiffer Iowa 

Patterson, Donald Malcolm New Jersey 

Potterfield, Garland Blair WestVirginia 

Sands, Paul Douglass [P.D.] Pennsylvania 

Shumaker, Henry Ward Pennsylvania 

Smith, John Preston Pennsylvania 

Spangler, Edwin Royer Pennsylvania 

Starr, Miss Mabel Connecticut 

Stein, Joseph Pennsylvania 

Wallace, William Romine Pennsylvania 



Award of Prizes. 
The Martin Cup, awarded to the graduation class obtaining a 
higher average than the one immediately preceding it, was awarded 
to the class of 1914 and accepted on behalf of the class by their 
president, Elwyn J. Wheeler, the presentation being made by Presi- 
dent French. 

The Welcome Cup, awarded to the second year class attaining 
a higher general average than the preceding class holding it, was 
awarded to the class of 191 5, and was accepted on behalf of the 
second year class by their president, William R. Tenney, the presen- 
tation being made by President French. 

" The Graduate 191 3 " Cup, awarded to the Freshman class for 
high general record in scholarship, and to be competed for by suc- 
ceeding Freshman classes, was for the first time presented to the 
Freshman class of this year and accepted on behalf of the class 
by their president, Harvey V. Stokely, the presentation being made 
by Joseph F. Elward, P.D., of the class of 19 13. 

The grade of distinguished was obtained by Stanley E. Sutton. 
The following attained the grade of meritorious: W. D. Balliet, 
L. Cohen, E. S. La Wall, W. R. Wallace, A. C. Webb, A. Weinstem. 

The William B. Webb Memorial Prize, a gold medal and certifi- 
cate, offered for the highest general average in the branches of 
Committee, Operative Pharmacy and Specimens, was awarded to 
Stanley E. Sutton, the presentation being made by Joseph L. 
Lemberger. 

The Chemistry Prize, $25, offered by Prof. Samuel P. Sadtler, 
for knowledge of Quantitative Chemical Analysis, was awarded to 
William R. Wallace. Edgar S. La Wall received honorable men- 
tion in connection therewith. 

The Materia Medica Prize, $25, offered by Prof. Clement B. 
Lowe, for the best examination in Materia Medica and in recog- 



336 Philadelphia College of Pharmacy. { Am j u J i y UI i 9 u arni ' 

nition of Materia Medica Specimens with a meritorious thesis, was 
awarded to Anton Hogstad, Jr. The following graduates received 
honorable mention in connection therewith : Woods D. Balliet, 
Edgar S. La Wall, Elmer F. Merz, Nervin A. Myers, Stanley E. 
Sutton, Alvin C. Webb and Elwyn J. Wheeler. 

The Microscopic Research Prize, a compound microscope, of- 
fered by Prof. Henry Kraemer, for the most meritorious thesis 
involving original microscopic work, was awarded to Anton Hog- 
stad, Jr. The following graduates received honorable mention in 
connection therewith : Edmund E. Carr, Daniel J. Fry, Jr., William 
W. Heckenberger, Frank L. Kahler, Walter M. KaufTman, Norris D. 
Rowland, Edwin R. Spangler and Alvin C. Webb. 

The Analytical Chemistry Prize, $25, offered by Prof. Frank X. 
Moerk, for the best work in qualitative and quantitative analysis, 
was awarded to William R. Wallace. The following graduates 
received honorable mention in connection therewith : Stanley E. 
Sutton and Alvin C. Webb. 

The Operative Pharmacy Prize, $20 in gold, offered by Prof. 
Joseph P. Remington, for the best examination in Operative Phar- 
macy, was awarded to Stanley E. Sutton. The following graduates 
received honorable mention in connection therewith : Woods D. 
Balliet, Charles F. Kutteroff, Forrest S. Marshall, Edwin R. 
Spangler, Alvin C. Webb and Fred C. Wolverton. 

The Maisch Botany Prize, $20 in gold, offered by Mr. Joseph 
Jacobs, of Atlanta, Ga., was awarded to Alvin C. Webb, the presen- 
tation being made by Professor Kraemer. The following graduates 
received honorable mention in connection therewith : Edmund E. 
Carr, Daniel J. Fry, Jr., Walter M. Kauffman and Edwin R. 
Spangler. 

The Mahlon N. Kline Theoretical Pharmacy Prize, a Troemner 
Agate Prescription Balance, for the best examination in Theory and 
Practice of Pharmacy, was awarded to Stanley E. Sutton, the pres- 
entation being made by Joseph W. England. 

The Commercial Pharmacy Prize, $20 in gold, offered by Prof. 
Joseph P. Remington to the graduate who passed the best examina- 
tion in Commercial Training at the final examination for the degree, 
was awarded to John C. Gehrung, the presentation being made by 
Prof. E. Fullerton Cook. The following graduates received hon- 
orable mention in connection therewith : Joseph F. Botdorf , Louis 
Cohen, Meyer C. Epstein, Nervin A. Myers, Stanley. E. Sutton, 
Alvin C. Webb and Elwyn J. Wheeler. 



Ain. Jour. Pharin. 
July, 1914. 



Serial Number Abolished. 



337 



The Instructors' Prize, $20, offered by the Instructors of the 
College, for the highest term average in the branches of Pharmacy, 
Chemistry and Materia Medica, was awarded to Stanley E. Sutton, 
the presentation being made by Prof. F. P. Stroup. The following 
graduates received honorable mention in connection therewith : 
Charles L. Gantert, Anthony LaCourse, Jr., Leo T. Trambley, Alvin 
C. Webb, Abram Weinstein and Elwyn J. Wheeler. 

The Pharmacy Quiz Prize, one year's membership in the Ameri- 
can Pharmaceutical Association, offered by Prof. Charles H. LaWall, 
for the best term work in Theory and Practice of Pharmacy, was 
awarded to Alvin C. Webb. The following graduates received 
honorable mention in connection therewith : Charles L. Gantert, 
Stanley E. Sutton, Leo T. Trambley, Abram Weinstein and Elwyn 
J. Wheeler. 

The Special Lecture Report Prize, $10 in gold, awarded for the 
best written reports of the series of special lectures held under the 
auspices of the College, session 1913-1914, was awarded to Charles F. 
Kutteroff, the presentation being made by Dr. A. W. Miller. The 
following graduates received honorable mention in connection there- 
with : Louis Cohen, Charles L. Gantert, Anton Hogstad, Jr., and 
Maurice Rosoff. 

The Kappa Psi Fraternity Prize, a gold medal, offered by the 
Eta Chapter of the Kappa Psi Fraternity to the graduate making the 
highest general average during the senior year at the College, was 
awarded to Stanley E. Sutton, the presentation being made by George 
L. Holstein. The following graduates received honorable mention in 
connection therewith : Edgar S. LaWall, Alvin C. Webb and 
Elwyn J. Wheeler. 



LEGEND AND SERIAL NUMBER ON INSECTICIDES AND 
FUNGICIDES ABOLISHED. 

The Three Secretaries Find that Guaranty Legend on Substances Used 
to Destroy or Prevent Insects and Fungi is Deceptive and Mis- 
leading. No More Serial Numbers to be Issued or Guaranties 
Accepted. 

Following their action prohibiting the use of a serial number 
and holding the guaranty legend on foods and drugs, under the 
Food and Drugs Act, to be deceptive, the Secretaries of the 
Treasury, Agriculture and Commerce, on June 30, signed an amend- 



338 



Serial Number Abolished. 



Am. Jour. Pharm. 
July 1914. 



ment to the regulations under the Insecticide Act abolishing the use 
of serial numbers on insecticides and fungicides. The amended 
regulation also holds that the use of the legend " Guaranteed by 
(name of guarantor) under the Insecticide Act of 1910," on the 
labelling of insecticides and fungicides, or similar legends is mis- 
leading and deceptive in that the public is induced by such legend 
and serial number to believe that the articles to which they relate 
have been examined and approved by the Government. 

The regulations, therefore, provide that the use of the guaranty 
legend or any similar legend on labels or packages of insecticides or 
fungicides, under which are included all substances for destroying 
or preventing insects or fungi affecting plants and animals, should be 
discontinued. 

The new regulation is to become effective on and after May 1, 
1916. In the case of products packed and labelled in accordance 
with the Insecticide Act and in conformance with the rules and 
regulations, prior to May i, 191 6, the amendment wiM become ef- 
fective on and after November 1, 1916. Manufacturers, however, 
need not wait until May 1, 191 6, to change their labels, but are free 
to make them conform to the new regulations at any time. 

As in the case of the ruling on foods and drugs, the amended 
regulation as to insecticides and fungicides provide that where a 
wholesaler, manufacturer or jobber wishes to guarantee his goods 
so as to protect the dealer from prosecution, he may incorporate 
this guaranty in or attach it to the bill of sale, invoice, bill of lading, 
or other schedule. As the protection of the dealer and not a guaranty 
to the consumer was the original purpose of the legend, the new 
method fully protects the dealer without misleading the consumer. 

In the meantime, the Department notifies the public that the 
presence of a serial number or guaranty legend on foods and drugs, 
or on insecticides and fungicides, in no way implies that the Govern- 
ment has tested or approved such articles, or guarantees them to be 
in compliance with the Federal law. 

Office of Information . , 

U. S. Dept. of Agriculture, 
Washington, D. C. 




THE AMEKICAN 



JOURNAL OF PHARMACY 



A CRITICISM OF THE UNITED STATER PH ARM ACp N ^T A 
WITH RESPECT TO THE NAMlN5Q^FNTfi^K>M- 
POUND, C 17 H 21 N0 4 .HBr + 3 H 2 0, AND WITH REGARD 
TO THE PRESCRIBED TESTS FOR ITS IDENTITY AND 
PURITY. 



Director of the School of Pharmacy, University of the Philippines. 

On the Origin and Usage of the Terms Hyoscine and 
Scopolamine. 

The term " hyoscin " was first used by Reichardt and Hohn 1 in 
1871 to designate a basic substance, C 8 H 15 N0 2 , obtained by the action 
of barium hydroxide upon hyoscyamine. In 1880, Ladenburg 3 iso- 
lated an alkaloid from the mother-liquor obtained in the preparation 
of the so-called amorphous hyoscyamine from the seeds of Hyoscya- 
mvis niger.* Ladenburg found the composition of this base to be repre- 

1 Ann. d. Chem. (1871), 157, p. 107. 

2 Later, the composition of this basic substance was found to be CSH13NO2 
and became known under various names, in accordance with the fancies of 
the respective investigators — " pseudotropin " (Ladenburg), " oxytropin " 
(Ladenburg and Roth), " scopolin " (E. Schmidt), and " oscin " (Hesse). 

The esters of the base CsHisNO;, the acetyl-, benzoyl-, and cinnamyl- 
esters were manufactured by the firm of E. Merck previous to the year 
1898, and were sold under the name of " Scopoleins," with the name of the 
acid radical as a prefix, e.g., " acetyl-scopolein." — Arch. d. Pharm. (1898), 
236, p. 33- 

3 Ber. d. deutsch. chem. Ges. (1880), 13, p. 1549. 

4 Bucheim was probably the first investigator to isolate the so-called 
" hyoscin." He obtained two basic substances from the seeds of Hyoscyamas 
niger, one of which he describes as being amorphous and oily, the other as 
being crystalline. To the former he gave the name " hyoscyamin " and to the 
latter the name " sikeranin." Cited by Ladenburg, Ann. d. Chem. (1881), 
206, p. 283. 



AUGUST, i 9 U 




By A. G. DuMez, 



(339) 



340 Criticism of U. S. Pharmacopoeia, { A \ n J g Zt' iml m ' 

sented by the formula, C 17 H 23 N0 3 , and thought it to be isomeric 
with hyoscyamine and atropine. He called it " hyoscin," as the 
compound obtained by Reichardt and Hohn was then thought to be 
identical with tropin, a decomposition product of hyoscyamine. In 
1888, E. Schmidt and Henschke 5 obtained an alkaloid from the root 
of Scopolia japonica, 6 which, from the analysis and properties of its 
aurichloride, they concluded was identical with the " hyoscin " of 
Ladenburg. A year later, Bender 7 - isolated hyoscyamine and what 
he thought was a new crystalline base from the root of Scopolia 
atropoides. A quantity of this crystalline base was sent to E. Schmidt 
for analysis. Bender describes the properties of this alkaloid as 
found by Schmidt under the name " scopclm.' 1 The analysis of 
the product led Schmidt to review carefully his former work on the 
base obtained from Scopolia japonica, with the result that he found 
the composition to be C 17 H 21 N0 4 8 instead of C 17 H 23 N0 3 , and that 
it was identical with the substance received from Bender. He gave 
it the name " scopolamine' Furthermore, Schmidt succeeded in 
obtaining this base, C 17 H 21 N0 4 , from several other solanaceous 
plants and also from commercial hyoscine hydrobromide, which 
was then being prepared by the firm of E. Merck. In fact, a base 
having the formula C 17 H 23 N0 3 and corresponding to Ladenburg's 
" hyoscin " could never again be isolated from the mother-liquor 
resulting in the crystallization of hyoscyamine, its absence being 
conclusively proven by L. Merck 9 in 1897. 

During the period of fifteen years following the work of Bender, 
the literature contains a considerable number of publications which 
tend to prove or disprove the identity of scopolamine and hyoscine, 

5 Arch. d. Pharm. (1888), 226, p. 185. 

6 Langaard, in 1880, reported the isolation of two alkaloids from the 
root of Scopolia japonica, which he named " scopoleine " and " rotoine " 
respectively. — Pharm. Jonrn. (1881), n, p. 10. 

Three years later, Eykman, working with the same root, reported the 
presence of but one alkaloid, to which he also gave the name " scopolein." 
The base isolated according to the method of Eykman was being prepared and 
marketed by Merck of Darmstadt and Schuchardt of Gurlitz as early as 
1888. Upon analysis, Schmidt found the product to be a mixture of " hyoscin " 
(Ladenburg), hyoscyamine, and atropine. — Arch. d. Pharm. (1888), 226, p. 
187. 

7 Chcm. Zeitung (1890), p. 805. 

8 Arch. d. Pharm. (1892), 220, p. 207. 

8 Journ. Soc. Chcm. Industr. (1897), T 6, p. 515. 



Am \n»Ts[; i P 9i4 rm '} Criticism of U. S. Pharmacopoeia, 341 

some of which also tend to show the desirability of establishing the 
usage of the term scopolamine in preference to hyoscine, or vice 
versa. The controversy was carried on principally by O. Hesse and 
E. Schmidt, with an occasional opinion from others. 

In 1892, when Hesse 10 published his results on the identification 
of the Solanaceous alkaloids, he agreed with Schmidt that the com- 
position of "hyoscin" (Ladenburg) should be represented by the 
formula C 17 H 21 N0 4 and that it was identical with " scopolamin," 
but objected to the introduction of the latter term, as the hydro- 
bromide had already been marketed for ten years under the name of 
" hyoscinhydrobromid." Later, however, Hesse concluded that the 
two were not identical, as 4k hyoscin " was known to be lsevo rotatory, 
and he succeeded in isolating a quantity of an optically inactive base 
from commercial scopolamine hydrobromide. This led him to be- 
lieve that " scopolamin " was a mixture of " hyoscin " and the new 
base to which he gave the name " atroscin." 11 As early as 1890, 
Schmidt 12 observed that the hydrobromide was laevorotatory. He 
also discovered that solutions of the active scopolamine hydro- 
bromide could be rendered optically inactive by the addition of 
small quantities of sodium or potassium hydroxide. This change 
he attributed to the conversion of the optically active base into an 
inactive isomer, 13 which he later isolated and called " inactive scopo- 
lamin." The identity of " atroscin " (Hesse) with the latter was 
conclusively proven by the work of Gadamer 14 and Kuntz-Krause 15 
respectively. 

The alkaloid represented by the formula, C 17 H 21 N0 4 , was first 
placed upon the market in the form of the hydrobromide by Merck 
of Darmstadt. It was then being prepared from the base isolated 
from the seeds of Hyoscyamus niger and was sold under the name 
of " hyoscinhydrobromide." About 1894, shortly after the work of 
Bender and Schmidt, scopolia root became recognized as a source 
of supply. However, the hydrobromide, when prepared from the 
base obtained from the latter source, was marketed as " skopolamin- 

10 Ann. d. Chcm. (1892), 271, p. 111. 

11 Bcr. d. deutsch. chcm. Ges. (1896), 29, p. 1781. The term "atroscin" 
has never received recognition by other investigators. 

12 Arch d. Pharm. (1892), 230, p. 207. 

13 Ibid. (1894), 2 32, p. 409- 
"Ibid. (1898), 236, p. 382. 

ir 'Journ. f. prakt. Chcm. (1910), 64, p. 569. 



342 Criticism of U. S. Pharmacopoeia. \ km i*™*{ Si™ 1 

hydrobromid." Thus, E. Merck, 10 in 1896, remarked that the alka- 
loids, hyoscine and scopolamine, were identical, but that the name 
hyoscine was given to the base when isolated from Hyoscyamus 
niger, while the term scopolamine was applied to that isolated from 
scopolia root. 

In 1897, L. Merck 17 called attention to some observations in- 
dicating that the hydrobromide prepared from the alkaloid obtained 
from Hyoscyamus niger was fairly constant, showing a specific 
rotatory power of — 24 to — 25 ; while that prepared in a 
like manner from the alkaloid when obtained from scopolia root 
varied and showed a much lower specific rotatory power, — I3.47°. 1S 
From the foregoing observations one would naturally infer that 
the designation hyoscine hydrobromide would insure a product 
strongly lsevorotatory and containing little of the optically inactive 
isomer, while the term scopolamine hydrobromide would indicate a 
salt having a low specific rotatory power. Such, however, is not the 
case, exactly the reverse being true at the present time. The observa- 
tions of Schmidt, 19 Hesse,- Luboldt, 21 and others show that the 
commercial salt, the hydrobromide, regardless of its natural source, 
often varied in its rotatory power. Schmidt attributed this variation, 
in the case of the salt prepared from Hyoscyamus niger, to the use of 
strong alkalies, such as the hydroxides of sodium and potassium, or 
even their normal carbonates on long standing, in the isolation of 
the free base. Furthermore, it was found that the name given to 
the commercial product was no indication of this variation, the salt 
designated hyoscine hydrobromide varying as well as that bearing 
the name scopolamine hydrobromide. However, upon the introduc- 
tion into the German Pharmacopoeia 22 of the term " Skopolamin- 

la Merck's Bericht (1894), p. 94. 

" Journ. Soc. Chem. Industr. (1897), 16, p. 515. 

ls Schmidt noted a specific rotatory power of -25 43' for scopolamine 
hydrobromide prepared from the base obtained from the root of Scopolia 
atropoides. He is of the opinion that the low rotatory power observed by 
Merck was due to the presence of i-scopolamine which may preexist in the 
plant at certain seasons of the year or which may be formed in the process 
of curing. — Arch. d. Pharm. (1898), 236, p. 59. 

w Apoth. Ztg. (1896), 11, p. 260. 

20 Ibid. (1895), 10, p. 187. 

21 Arch. d. Pharm. (1898), 236, pp. 11-47. 

22 Deutsches Arzneibuch, 5th Edit., Berlin (1910), p. 451. 



Am Augu U st* i P 9H rm '} Criticism of U. S. Pharmacopoeia, 343 

hydrobromid " with the specific rotatory power as a test for its 
identity and purity, German manufacturers began producing the 
lsevo-salt to the exclusion of that having little or no rotatory power. 
Hence the name scopolamine hydrobromide, in Germany at least, now 
signifies the lsevo-compound. 

That the present tendency in England is to apply the name 
scopolamine hydrobromide in a manner similar to that of the Ger- 
man Pharmacopoeia, while hyoscine hydrobromide is being used 
to designate the salt having the weaker rotatory power, is evidenced 
in the following: 

(a) Spencer Sheill 23 states that scopolamine is used by some to 
represent the laevo-compound, while hyoscine is applied by others to 
the mixture of the lsevo- and inactive varieties having the weaker 
rotatory power. 

(b) A statement similar to the latter is also given in the Extra 
Pharmacopoeia of Martindale and Westcott. 24 

(c) Finnemore and Braithwaite 25 report that English physicians 
use the term scopolamine hydrobromide when prescribing rather 
than hyoscine hydrobromide in order to be sure of securing the 
German preparation, which is lsevorotatory. 

From the survey of the literature, it appears that the designation 
hyoscine hydrobromide is still given preference in the United States, 
although practically all of the salt is imported from Germany and is 
now being received largely as the lsevo-variety. 

A more concrete idea of the variations in the naming of the alka- 
loid and its salt, the hydrobromide, may be obtained from the 
following tabulations : 

TABLE NO. 1. 

Names Applied to the Free Base or Related Compounds. 



Atroscin. 



Hyoscin . 



Hesse, 1896 = Ci7H 2 iN0 4 , isolated from commercial scopolamine 
hydrobromide, optically inactive and identical with 
i-scopolamine. 

Reichardt and Hohn, 1871 =C s Hi 5 NO, a decomposition product of 
hyoscy amine. 

Ladenburg, 1880 = CnH23N0 3 , isolated from Hyoscyamus niger. 
Schmidt and Henschke, 1 888 = a base isolated from Scopolia japonica. 
Hesse, 1892 = C17H21NO4, isolated from Hyoscyamus niger. 
E. Merck, 1894 = Ci7H 2 iN04, isolated from Hyoscyamus niger. 



23 Lancet (1910), 11, p. 29. 

24 Martindale and Westcott, Extra Pharmacopoeia, London (1912), p. 444. 

25 Year-Book of Pharm. and Trans. (1912), p. 498. 



344 



Criticism of U. S. Pharmacopoeia. 



( Am. Jour. Pharm. 
( August, 1914. 



Scopolamin. 



Inactive 
Scopolamin. 

Scopoleine. . 

Scopoleins. . 
Scopolin. . . . 



Schmidt, 1890 = Ci7H 2 iN0 4 , isolated from Scopolia japonica. 
Schiitte, 1 89 1 =Ci7H2iN0 4 , isolated from Datura stramonium. 
Schmidt, 1892 = Ci 7 H 2 iN0 4 , isolated from Datura stramonium, Du- 

boisia myoporoides, and Atropa belladonna. 
E. Merck, 1894 = d 7 H 21 N0 4 , isolated from Scopolia root. 
Thorns and Wentzel, 1898 = C17H21NCX1, isolated from Mandragora 

root. 

Schmidt, 1896 = Ci7H 2 iN0 4 , the optically inactive isomer. 

fLangaard, 1881 =a mixture of alkaloids from Scopolia japonica, 

\ principally C ]7 H 2 iN0 4 . 

<! Firm of Merck, 1898 = esters of the base, C 8 Hi:jN0 2 . 

-{Bender, 1890 = CnH 2 iN0 4 , isolated from Scopolia japonica. 

TABLE NO. 2. 



Official Names and Synonyms of the Hydrobromide. 



British Pharmacopoeia, 1898. 



Hyoscinae hydrobromicum 

Hyoscine hydrobromide 

Hydrobromate of hyoscine 

Scopolamine hydrobromide 

Hyoscinae hydrobromidum 

Hyoscine hydrobromide 

Hyoscinae hydrobromas, 1890 ^United States Pharmacopoeia, 1905. 

Scopolaminae hydrobromidum | 

Scopolamine hydrobromide J 

Neither the free base nor its salt, the hydro- \™ , ^ 

bromide, is official : ... . j French Pharmacopoeia, 1908. 

Bromidato di Scopolamina ^Italian Pharmacopoeia, 1909. 

IS^^dS^ micum :::::: : : : :} G — p— op^a, t9I0 . 

On the Physiological Action of Scopolamine. 

Scopolamine is an ester of tropic acid and the base, scopolin, 20 
and, like the closely related hyoscyamine, may exist in three stereo- 
isomeric forms. Two of these, the kevo- and racemic forms, are 
known. These isomers, like those of nicotine 27 and hyoscyamine, 28 
differ in their physiological action as well as in their chemical and 
physical properties. 

The early investigators who attempted to discover a difference in 
the physiological action of the two isomers did not work with the 
material prepared in their own laboratories, and very probably 
used the salts in an impure state ; i.e., as mixtures of the two isomers 
or with small amounts of other impurities 29 present. Add to this 

2t; Gadamer, Arch. d. Pharm. (1901), 239, p. 321. 

27 Ber. d. deutsch. chem. Ges. (1904), 37, p. 1234. 

28 Cushny, Journ. of Physiol. (1904), 30, p. 176. 

29 Schmidt, Scopolamine hydrobromide with a low specific rotatory power 
contains a small amount of an impurity not easily detected. — Arch. d. Pharm. 
(1905), 243, p. 4. 



Am Augu U st' i9 h ii m '} Criticism of U. S. Pharmacopoeia, 345 

the lack of chemical knowledge concerning the substance with 
which they were working and we can readily understand why they 
obtained varying and sometimes contradictory results. 

Konigshoefer 30 reported that the effect of atroscine (i-scopo- 
lamine) upon the accommodation takes place with greater rapidity 
and is of longer duration than in the case of scopolamine (1- 
scopolamine). Under pathological conditions (iritis) he also found 
its action to be the more energetic. 

Meyer confirmed 31 the latter finding, but stated that he could not 
agree with Konigshoefer with respect to the action on the accommoda- 
tion. 

Uhthoff and Axenfeld 32 could find no difference in the physiologi- 
cal action of scopolamine hydrobromide having a specific rotatory 
power of — 25. 43 and that having specific rotatory power of 
— 6.62 . 

In more recent years the work has been taken up with a greater 
knowledge of the chemistry of the isomers and under more ad- 
vantageous conditions, with the result that real differences in their 
physiological activity have been found and clearly described. 

Cushny and Peebles 33 found : 

(a) That the action of 1-scopolamine on the terminations of the 
secretory nerves in the salivary glands and on the terminations of 
the inhibitory fibres of the heart was double that of i-scopolamine 
in effect; from which they inferred that a similar ratio might hold 
in other analogous terminations. 

(b) That 1- and i-scopolamine produce the same effect in a like 
degree upon the central nervous system in man and mammals and 
on the terminations of the motor nerves in the frog. 

E. Hug, 34 from a series of experiments On dogs and cats, con- 
cluded : 

(a) That the action of 1-scopolamine on the vagus is three to 
four times as great in strength as that of i-scopolamine. 

(b) That 1-scopolamine acts twice as energetically as i-scopo- 
lamine upon the oculomotorius. 

Evidence to the effect that a difference in the physiological action 

30 Cited by Hesse, Ber. d. deubsch. chem. Gcs. (1896), 27, p. 1781. 

31 Cited by E. Schmidt, Arch. d. Phar, (1897), 236, p. 71. 

32 Cited by L. Merck, Pharm. Journ. (1897), 71, p. 41, 

33 Joum. of Physiol. (1905), 32, pp. 501-510. 

34 Arch. f. exp. Path. u. Pharmak. (1912), 69, p. 56. 



346 



Criticism of U. S. Pharmacopoeia, 



Am. Jour. Pharm. 
August, 1914. 



of the commercial preparations has been observed by medical practi- 
tioners is amply supplied in the literature. In fact, the references 
are too numerous to be included in this paper. However, the state- 
ment of Finnemore and Braithwaite 35 in connection with the use of 
hyoscine and scopolamine hydrobromides by English physicians is 
quoted because of the direct application : 

" Anaesthetists have expressed a preference for the German 
preparations sold under the name of ' Scopolamine hydrobromide ' 
owing to the variable results obtained following the administration 
of the product known as ' Hyoscine hydrobromide.' 

On the Tests eor Identity and Purity. 

The chemical and physical properties of scopolamine and its 
salts have been quite thoroughly worked up by E. Schmidt, O. Hesse, 
Gadamer, and others. There is, however, some uncertainty con- 
cerning the melting-points of the chloraurates of both the 1- and i- 
scopolamine, the greater number of the investigators confirming the 
results obtained by Schmidt. The following tables show the im- 
portant physical constants of the hydrobromides as obtained by 
various investigators and as given in the United States, British, and 
German Pharmacopoeias : 

TABLE NO. 3. 



Name of 
investigator. 


Stero- 
isomer. 


M. P. of 

the anhy- 
drous salt. 


M. P. of 

the chlo- 
raurate. 


M. P. of 

the hydro- 
brom-chlo- 
raurate. 


M. P. of 
the picrate. 


Specific ro- 
tatory 
power in 
aqueous 
solution. 


E. Schmidt* 


Laevo- 
Inactive 
Inactive 
Lsevo- 


193-194° 
i8o° 


212-214 
208-210 

208° 

208-209 
205° 

198° 

201-202° 




187-188° 


-25° 43' 

0° 
0° 

-2 5 °52' 


E. Schmidt 










Kircher 38 








Thorns and Wentzel 39 . 
0. Hesse 40 









Laevo- 

Inactive 
Laevo- 


192-197 
181 






-25. 7° to 
-25-9° 

0° 


0. Hesse 






Jowett 41 


About 215 















35 Year-Book of Pharm. and Trans. (1912), p. 498. 

36 Arch. d. Pharm. (1898), 236, p. 59. 

37 Ann. d. Chem. (1900), 310, p. 352. 

38 Arch. d. Phar. (1905), 243, p. 321. 

39 Ber. d. deutsch. chem. Gcs. (1898), 31, p. 2037. 

40 Journ. f. prakt. Chem, (1901), 64, 2, p. 364. 
^Journ. Chem. Soc. (1897), 71, p. 678. 



Am. Jour. Pharm. 
August, 1914. 



Criticism of U. S. Pharmacopoeia, 



347 



In explanation of the table it should be stated that Schmidt and 
Gadamer determined the melting-points of the various salts, using a 
capillary tube and sulphuric acid bath ; Hesse used a " Roth's " 
apparatus. Schmidt found the melting-point of the chloraurate of 
the 1- salt to be 208 ° to 209 when determined with the " Roth's " 
apparatus. 42 

TABLE NO. 4- 



Pharmacopoeia. 


Per cent, of H2O lost in dry- 
ing at ioo° C. or over H2SO4 


M. P. of the 
anhydrous salt. 


M. P. of the 
chloraurate. 


Specific rota- 
tory power of 
a 5 per cent, 
aqueous solu- 
tion at 15° C 


United States 43 . . 
British 44 




179-7° 
1 93- 1 94° 
About 190 


197° 
198° 




More than 12 per cent. 
12.3 per cent. 




German 45 


-24° 45' 





A comparison of the constants as given in Tables No. 3 and No. 4 
shows the melting-point (179.7 C.) of the anhydrous hydrobromide 
as specified in the United States Pharmacopoeia to agree very closely 
with that (180 C.) found by Schmidt or Hesse (181 C.) for i- 
scopolamine hydrobromide; while the melting-point (197 C.) of 
the chloraurate as given in the pharmacopoeia corresponds very well 
with that (198 C.) found by Hesse for the chloraurate of 1-scopo- 
lamine. According to two observers, the melting-point of the hydro- 
bromide alone is no indication as to the respective quantities of the 
1- and i-isomers present in the commercial salt ; e.g., Schmidt 46 found 
a melting-point of i8o°-i8i° C. for the commercial hydrobromide, 
[a]D = — 13 30'; Hesse 47 obtained a melting-point of 178 C. for 
a sample of the hydrobromide, [a]D = — 21. 3 . If we take into 
consideration the fact that the hydrobromides of both the lsevo- and 
the inactive forms crystallize with 3H0O, and that the melting-points 
of the chloraurates have not yet been definitely established, it be- 
comes evident that the pharmasppoeial tests for the identity of this 
compound are worthless. 

That physical constant which has been found to give the most 
accurate indication as to the purity of 1-scopolamine or its salts, 



42 Arch. d. Phar. (1894), 232, p. 417. 

43 U. S. P., 8th Rev. (1905), P- 39L 
"British P. (1898), p. 153. 

45 Deutsches Arzneibuch, 5th Edit., Berlin (1910), p. 451. 

48 Arch. d. Pharm. (1898), 236, p. 62. 

47 Jour n. f. prakt. Chan. (1901), 64, 2, p. 385. 



348 Criticism of U. S. Pharmacopoeia. -j An ^ u ^J- ^ rm ' 

both with respect to the presence of the inactive variety and to 
foreign substances, is the specific rotatory power. This has been 
found to be between — 24 and — 25 for the fairly pure 
anhydrous hydrobromide in a 5 per cent, aqueous solution at 15 C. 
A specific rotatory power of — 32. 3 to — 32.9 has been found 
by Hesse 48 for the salt in a high state of purity. Determinations 
of this constant have revealed the following variations in the 
commercial product: 

1894 — E. Schmidt 49 : Scopolamine hydrobromide from Gehe and Com- 
pany, Dresden, [a] D = — 14.58 °. 

1895 — E. Schmidt 50 : Scopolamine hydrobromide from E. Merck, Darm- 
stadt, [a] D = — 17 9'. 

1895 — Gadamer 51 : Scopolamine hydrobromide from Gehe and Company, 
Dresden. Anhydrous salt in aqueous solution, p = 6.3043, t = 19.8 C, 
[a] D = — 6.62°. 

1896 — O. Hesse 52 : Five commercial samples of scopolamine hydrobromide 
showed a specific rotatory power as follows: — 22.1 °, — 12.7 °, — 12. 1 °, 
— 11.3 °, — 10.0 °. 

1897 — L. Merck 53 : Scopolamine hydrobromide from Scopolia root, 
[a] D = — 13-47°. Scopolamine hydrobromide from the seed of Hyoscyamus 
niger, [a] D = — 24 to — 25 . 

1898 — Luboldt 54 : Scopolamine hydrobromide from Gehe and Company, 
Dresden. 1.5304 Gm. of anhydrous salt in aqueous solution, d = 1.0096, 
t = i 5 °, [a] D = i 4 ° 58'. 

1899 — O. Hesse 55 : Scopolamine hydrobromide, commercial. Anhydrous 
salt in aqueous solution, p = 4, t = 15 , [a] D= — 7.5 . 

1901 — Gadamer 56 : Scopolamine hydromide from E. Merck, Darmstadt. 
[ a ] D = — 24.69°. 

1912 — E. Hug 57 : Scopolamine hydrobromide from Hoffmann-La Roche 
Company, Grenzach. Anhydrous salt in aqueous solution, p = 4.5, [a] D 
= — 26.0°. 

1912 — Finnemore and Braithwaite 58 : Four samples of commercial hyoscine 
hydrobromide showed a specific rotatory power as follows: —23° 7', — 21 
59', — 21° 25', — 6° 30'; one sample was found to be inactive. 

is Joum. f. prakt. Chem. (1901), 64, 2, p. 385. 
4 »Apoth. Ztg. (1896), 11, p. 260. 
60 Ibid. 

51 Cited by Schmidt, Arch. d. Pharm. (1898), 236, p. 47. 
52 Ber. d. dentsch. chem. Gcs. (1896), 29, p. 1780. 
63 lourn. Soc. Chem. Industr. (1897), 16, p. 575. 

54 Arch. d. Phar. (1898), 236, p. 14. 

55 Ann. d. Chem. (1899), 309, p. 90. 

56 Arch. d. Phar. (1901), 239, p. 324. 

"Arch. f. exp. Path. u. Pharmak. (1912), 69, p. 48. 
58 Phar. lourn. and Trans. (1912), p. 498. 



Al August' 1914™'} Constituents of Androgr aphis Paniculata. 349 

Conclusions and Suggestions. 

1. Practically all of the scopolamine hydrobromide or the so- 
called hyoscine hydrobromide consumed in the United States is at 
present supplied by Germany, where the laevo-compound only is 
recognized as official under the title " Skopolaminhydrobromid." In 
view of this fact, and as present usage, not only in Germany but in 
other continental countries and in England, indicates a preference 
for the latter term, there can be no important reason for the same 
compound appearing under two different titles in the United States 
Pharmacopoeia. It is therefore suggested that the term " Scopo- 
lamine hydrobromide " be made the official English title in the next 
revised edition of the pharmacopoeia, with " Hyoscine hydrobro- 
mide " as a possible synonym. 

2. As there is still some doubt concerning the exact melting- 
point of the chloraurate of either the 1- or i-scopolamine, this con- 
stant should not be prescribed as a test by the next pharmacopoeia. 

3. It is now known that scopolamine or the so-called hyoscine 
may exist in either the laevo- or inactive forms, and that the com- 
mercial hydrobromide is usually the lsevo-salt, but not infrequently 
a mixture of the two isomeric forms. It is also known that the 
isomers produce different physiological effects, the laevo- variety pre- 
ferred by medical practitioners because of its particular physiological 
action and on account of its constant state of purity. It is therefore 
suggested that the revised edition of the United States Pharma- 
copoeia recognize only the 1-scopolamine hydrobromide as official, 
and that a definite specific rotatory power be prescribed for it. 



CONSTITUENTS OF ANDROGR A PHIS PANICULATA. 

By KSHITIBHUSHAN BHADURI, M.Sc. 

Androgr aphis paniculata, Nees (Fam. Acanthacecc) , is a common 
bitter plant growing throughout the plains of India. The plant is an 
annual one, two to three feet long; stem quadrangular, pointed, 
smooth; leaves opposite, on short petioles, lanceolate, entire upper 
surface dark green and shining, under surface paler and finely 
granular; they vary much in size, but the larger are usually three 
inches in length and one inch in breadth ; calyx deeply five-cleft, 
corolla bilabiate, tips linear, reflected, upper one three-toothed, lower 



350 



Constituents of Andrographis Paniculata. 



Am. Jour. Pharm. 
August, 1914. 



one two-toothed; flowers remote, alternate, long petioles, downy, 
rose colored or white streaked with purple; capsules erect, some- 
what cylindrical ; seeds, three to four in each ; roots fusiform, simple 
woody with numerous fine radicles. 

The plant is well known in Bengal under the name of Kalmegh, 
and is the principal constituent of a domestic medicine named Alui 
which is given to children for the relief of griping, irregularity of 
bowels, and loss of appetite. It is also called Kiryat, and is used as 
a substitute for chirata. It is called in Sanskrit " Mahatikta," or 
king of bitters. 

According to Dr. W. A. Boorsma (Mededeelingen uit S Lands 
plantentium, 1896, xviii, 63), if the powdered plant be mixed with 
lime and submitted to steam distillation, the distillate gives all the 
tests of a volatile alkaloid which he could not isolate. He, however, 
isolated an amorphous bitter substance (C 15 H 27 4 ). 

He says that the substance begins to decompose before melting, 
so that he could not determine its melting-point accurately. The 
amorphous substance obtained by the present author has some 
properties common with the above substance, but the melting-point 
has been accurately determined ; while the above author says that 
the amorphous and crystalline (also obtained by him) substances 
have the same properties, the two substances described herein have 
very different properties. 

Dr. K. Gorter, by extracting the leaves of Andrographis panicu- 
lata with alcohol, obtained a lactone (C 22 H 30 O 5 ) named andrographo- 
lite. It is converted into salts of andrographic acid by boiling with 
caustic alkalies (Apoth. Zeits., 191 1, 26, 954). 



For examination 68 Gm. of the powdered leaves and stems were 
taken and exhausted in a Soxhlet apparatus successively by 
petroleum ether, ether, chloroform, and alcohol ; after evaporation 
of the solvents the extracts weighed: 



Experimental. 



Petroleum ether 

Ether 

Chloroform . . . 
Alcohol 



0.437 Gm., or 0.643 per cent. 
0.5864 Gm., or 0.861 per cent. 
2.2501 Gm., or 3.309 percent. 
1.5045 Gm., or 2.214 percent. 



Total 



7.027 per cent. 



Ab a4S" nu m '} Constituents, of Andrographis Paniculata. 351 

55 Gm. of substance on burning gave 9.7802 Gm. or 17.782 per 
cent, of ash. 

The plant is very rich in chlorophyll, one portion of which is 
soluble in chloroform and the other not, though both are soluble 
in alcohol. 



Examination of the Petroleum Ether Extract. 

This was a viscid, brownish-yellow colored liquid from which, 
on keeping a small quantity of an inactive, needle-shaped crystalline 
substance separated out, having 117 C. as its melting-point, the 
quantity obtained was so small that no further examination was 
possible. The viscid mass also contained a little essential oil, which 
was separated by extraction with alkalies ; the rest of it was " kalmegh 
resin," a portion of which was extracted by first making it alkaline 
with caustic potash and shaking up with ether. It can be further 
extracted with ether after acidification with an acid. 



Chloroform Extract. 

This contained besides chlorophyll an amorphous white substance 
and very little of a bitter substance, the former of which separated 
out on concentrating the chloroform extract. Its melting-point is 
221 C. It is tasteless and insoluble in water and alcohol. It is 
unacted upon by acids and alkalies. 



Extraction of the Bitter Principles. 

For this extraction the powdered leaves and stems were ex- 
hausted in a percolator with alcohol, almost the whole of which was 
distilled off. The thick, viscid mass left in the flask was then sub- 
mitted to steam distillation. Two or three drops of an essential oil 
first came over ; this had an intensely characteristic odor suggesting 
that of the dried plant. The distillation continued till the whole of 
the alcohol was distilled off. The residue remaining in the flask 
separated into two layers, one aqueous and the other solid ; the 
former when allowed to cool deposited some yellow colored crystals 
(bitter a) ; the latter was boiled with water and filtered hot; from 
the filtrate a white amorphous precipitate was deposited having an 
extremely bitter taste (bitter b). 



352 Constituents of Andrographis Paniculata. { Km jJ™' Jnf* 

Examination of the Bitter Principle (A). 

This was purified by dissolution in alcohol and fractional precipi- 
tation ; the process was repeated three times. It had a pale yellow 
color. When a little of the substance was heated in a test-tube it 
diffused a very fragrant odor. It had melting-point of 206 C. 

Strong sulphuric acid produced a yellowish-brown color. With 
potassium dichromate and sulphuric acid the substance at first gave 
a deep brown (almost black) color, attended with brisk effervescence. 
After a time the effervescence ceased and the color passed to grass- 
green. 

Strong sulphuric acid containing a trace of nitric acid produced 
a reddish-brown color. 

Strong sulphuric acid containing ammonium vanadate produced 
brownish-red color, changing to green. 

In strong nitric acid the substance dissolved readily, the solution 
acquiring a yellow color. 

The substance is very soluble in ethyl and methyl alcohol, though 
not to the above extent in amyl alcohol. It is very slightly soluble 
in chloroform and ether. Benzene and petroleum ether do not dis- 
solve it even on boiling. 

It is neither an alkaloid nor a glucoside, as it neither contains 
nitrogen nor produces a reducing sugar after hydrolysis. It can be 
acetylated, — i.e., it contains hydroxyl groups; the acetyl derivative 
is white and insoluble in water. Its melting-point is 95 ° C. 

When the substance was added to a solution of bromine in 
chloroform a dark-colored oil separated out; on washing the latter 
with a dilute solution of potassium carbonate a white solid substance 
was left behind. This was the bromo derivative of the bitter; 
the direct absorption of bromine proves the presence of at least one 
double bond. The melting-point of the bromo derivatives would not 
be determined, as it began to decompose at 120 C. before melting; 
at 160 C. it was a liquid, but began to give off a quantity of gas. 

0.0498 Gm. of the bromo derivative gave 0.0160 Gm. of AgBr 
or 13.7 per cent, of bromine. Since there must be at least two 
atoms of bromine in the molecule, the molecular weight is 1175 or 
some multiple of it. 

0.1008 Gm. of the bitter analysis gave 0.2521 Gm. of CO' 2 and 
0.0763 Gm. of H 2 0. 

Hence C 68.2, H 8.4. 



Am Au^"t* igu™'} Constituents of Andrographis Paniculata. 353 
The simplest formula is C 19 H 28 0; 5 . 

The molecular weight of the bitter principle as determined from 
the bromo-compounds is 1015, which is exactly six times that of 
the empirical formula. 

The acetyl derivative gave the following analytical data : 

It contains 1.74 per cent, of water. 

0.0697 Gm. of it gave 0.1863 Gm. of C0 2 and 0.05056 Gm. of 
H 2 0. 

Hence C 76.2 H 8.06. 

Examination of the Bitter Principle (B). 

It was a white amorphous substance having an extremely bitter 
taste. It is odorless, and its melting-point is 185 C. It is practi- 
cally insoluble in cold water. When a little of the substance was 
boiled for a long time with water the latter acquired a slightly acid 
reaction. It is soluble in alcohol and chloroform. In the Pharma- 
cographia of Fluckiger and Hanbury it is said that an infusion 
gives a voluminous precipitate with tannic acid, but this property 
was altogether found to be absent. Most probably in the former case 
the precipitate was due to the presence of some albuminous matter. 
Sulphuric acid produces an orangish-yellow color; when potassium 
dichromate is added to the above the color changes as one to yellow- 
green, which through greenish-brown finally passes to deep grass- 
green. If the substance be mixed with potassium dichromate before 
the addition of sulphuric acid, and the acid then added, the color 
first produced is brown, but the final color in this case also is deep 
grass-green. 

Strong sulphuric acid containing a trace of nitric acid gives a 
brown color. 

Strong sulphuric acid containing a trace of ammonium vanadate 
produces a brown color, changing to violet. 

Strong nitric acid does not produce any change. 

0.409 Gm. gave 0.0448 Gm. of H 2 and 0.0930 Gm. of C0 2 . 

C 62.01, H< 14.88 and O 23.01, 

The formula C 19 H 51 5 is given to it, for which the theoretical 
values are — 

C 62.24, H 14.7 O 23.01. 
The name Kalmeghin is proposed for it. 

A white substance separated out when bitter (b) was treated 
with an acid. 



354 On Determination of Acetanilid. { A ^udT ST™' 

This was washed with water and dried. It had an acid reaction 
and was soluble in alkalies, neutralizing it. As it was derived from 
Kalmeghin the name Kalmeghic acid was given to it. 

0.043 Gm. gave 0.0699 Gm. of H 2 and 0.2053 Gm. of CO.. 

Hence C 75.23 H 10.4. 

The formula is C 14 H 23 2 . 

This acid, as well as the bitter principle (b), gave fluorescein 
test, showing the presence of a benzine nucleus with two adjacent 
side chains. 

Chemical Laboratory, Presidency College, Bengal. 



ON THE DETERMINATION OF ACETANILID. 
By Dr. A. Mirkin, Cincinnati, Ohio. 

The determination of acetanilid in tablets is still effected by an 
extraction with chloroform, the chloroform being collected in a 
tared flask, evaporated, and the residue dried at a low temperature 
and weighed. This method frequently gives low results on account 
of the volatility of acetanilid, and very often it is not applicable at all 
on account of the presence of other ingredients in the tablets which 
are also soluble in chloroform. 

The volumetric method adopted by the Association of Official 
Agricultural Chemists, in which a solution of potassium bromide- 
bromate is used, does not always give accurate results, and it seemed 
desirable to find another method which might prove successful when 
other methods failed. 

Bay and Vignon (Comptes Rend., 135, 507; Centralblatt, 1902, 
ii, 1094) determine nitrous acid by titrating with a standard solution 
of aniline. The nitrous acid is used up in diazotizing the aniline. 
As soon as the nitrous acid is gone a piece of potassium iodide-starch 
paper, with which the solution is tested from time to time, does not 
turn blue any more. This reaction is reversible, and one can titrate 
aniline with a standardized solution of sodium nitrite. By convert- 
ing acetanilid into aniline and titrating with a standard sodium nitrite 
solution, we have a quick method of determination. In order to 
obtain correct results all the conditions mentioned below must be 
strictly adhered to. 



Am. Jour. Pharm. ) 
August, 1914. / 



Vleminckx's Solution. 



355 



One gramme of acetanilid is boiled for four hours with a mixture 
of one part sulphuric acid (sp. gr. 1.84) and five parts water. The 
solution is then cooled and carefully neutralized with sodium bicar- 
bonate. HQ is then added (6 mol. to 1 mol. anilin) and the flask 
is cooled to — io° by throwing in pieces of ice and using a freezing 
mixture. The sodium nitrite is then slowly added from a burette 
with thorough shaking of the flask after each addition. From time 
to time the solution is tested with potassium iodide-starch paper. It 
frequently happens that the potassium iodide-starch paper turns blue 
even when there is unchanged aniline. This is due to the low tem- 
perature, which causes the diazotizing to take place slowly. One 
must therefore not be too hasty in his conclusions, especially at the 
end, but wait several minutes after the addition of sodium nitrite 
before applying the Kl-starch paper test. 

As mentioned above, Bay and Vignon, the originators of this 
method, should be given full credit. I have only adapted their method 
of determining aniline to the determination of acetanilid. 



PREPARATION AND ANALYSES 1 OF VLEMINCKX'S 

SOLUTION. 1 

By Joseph L. Mayer. 

A short time ago two samples of Vleminckx's Solution were sub- 
mitted to me with a request that in view of the fact that the color of 
one sample was markedly different from the other, analyses be made 
to ascertain if they were properly prepared. 

Since the National Formulary only contains a formula for the 
preparation, and various pharmaceutical authorities consulted made 
no reference to a standard, it was necessary to make samples in an 
effort to determine how the solution should be prepared and what 
the strength of the finished product should be. The following work 
was therefore undertaken. 

Referring to page 81, 3rd edition of the National Formulary, 
we found that " Liquor Calcis Sulphuratse " — " Vleminckx's Solu- 
tion " — was directed to be prepared as follows : 

Lime, freshly slaked 165 grammes. 

Sublimed sulphur 250 grammes. 

Water, a sufficient quantity to make 1000 grammes. 



1 Read before the Kings County Pharmaceutical Society, May 12, 1914. 



356 



Vleminckx's Solution. 



/Am. Jour. Phartu. 
( August, 1914. 



Mix the slaked lime with the sulphur, and add the mixture grad- 
ually to 1750 c.c. of boiling water. Then boil the whole, under con- 
stant stirring, until it is reduced to 1000 grammes, strain, and having 
allowed the solution to become clear by standing in a well-stoppered 
bottle, decant the clear brown liquid, and keep it in completely filled 
and well-stoppered bottles. 

We accordingly made up one-tenth of this formula by taring a 
600 c.c. porcelain evaporating dish, adding 175 c.c. of water heating 
to boiling and then slowly adding the mixture of freshly slaked lime 
and sulphur, constantly stirring while heating until the weight was 
reduced to 100 grammes. The material was then decanted into a 
4 oz. cork stoppered bottle, allowed to stand until the next day, 
filtered and assayed for total sulphur by the following method: 

14 Measure 10 c.c. of the clear sample in a 100 c.c. measuring 
flask and fill to the mark. Analyze 10 c.c. aliquots of this solution. 
Treat with 3 c.c. of saturated solution potassium hydroxide or so- 
dium hydroxide solution, following by 50 c.c. hydrogen peroxide 
free from sulphates. Heat on the steam bath for one-half hour 
exactly and then acidify with hydrochloric acid, precipitate with 
barium chloride in the usual way in boiling solution, and finally 
weigh as barium sulphate." Of course multiplying the weight of 
barium sulphate by the proper factor gives the quantity of sulphur 
and this multiplied by 100 gives the percentage. 

We ran blanks on the reagents and determined the quantity of 
sulphate present, which was then deducted from that found in the 
actual analysis. 

This is Avery's method, and is suggested by the Association of 
Official Agricultural Chemists for the analysis of lime-sulphur dips 
and lime-sulphur-salt mixture (U. S. Dept. Agr. Bureau of Chem- 
istry, Bui. 107, rev. page 34) ; it is an extremely accurate and simple 
one which in our hands yielded remarkably close duplicates. 

We also analyzed the sample for total sulphur irr solution, mono- 
sulphur equivalent, thiosulphate sulphur, sulphate and sulphite sul- 
phur, total sulphide sulphur and total lime (CaO) in solution follow- 
ing the method in U. S. Dept. Agr. Bureau of Chemistry, Bui. 162, 
page 29, but seeing no advantage over the Avery method, employed 
that in all our analyses and simply determined the total sulphur, of 
which the above sample showed the presence of 10.838 grammes in 
100 c.c. of solution. 



Am. Jour. Pharm. ) 
August, 1914. / 



Vleminckx's Solution. 



357 



Another 100 gramme lot made up in the same manner contained 
14.581 grammes of total sulphur in 100 c.c. of solution. 

This great variation in results indicated difficulty in properly 
preparing the solution. We, therefore, referred to the direction in 
the N. F. and found it directed to add the lime and sulphur mixture 
" gradually to 1750 c.c. of boiling water. Then boil the whole 
under constant stirring until it is reduced to 1000 grammes ;" this 
procedure differs from mine in that it directs the water to be heated 
to boiling, the mixture of lime and sulphur added and the whole 
boiled under constant stirring until the weight is reduced to 1000 
grammes. 

Another 100 gramme lot was then made by strictly adhering to 
these directions and when assayed showed the presence of 4448 
grammes of total sulphur in 100 c.c. solution. 

My original reading of the process was as above noted to heat 
the water to boiling and then while the water was still on the fire 
to gradually add the lime and sulphur under constant stirring and 
boiling until the proper weight was produced, whereas the last prod- 
uct was made by strictly following the N. F. by heating the water 
to boiling, taking it off the fire, stirring all the lime and sulphur in, 
putting it back on fire, stirring and heating until the proper weight 
was attained. 

The above figures clearly indicated that the wording of the ma- 
nipulation in the N. F. was faulty, therefore another batch of 100 
grammes, employing the official quantities, was made by taring a 250 
c.c. Erlenmeyer flask, adding 175 c.c. of water heating on the hot 
plate until boiling and then adding the lime and sulphur previously 
mixed and boiling on the hot plate without stirring or further atten- 
tion until the weight was reduced to 100 grammes, transferred to a 
4 oz. cork stoppered bottle, allowed to stand until the next day, 
filtered and assayed. 

The solution contained 29.162 grammes of total sulphur in 
100 c.c. 

Another lot made by the same method contained 29.593 grammes 
of total sulphur in 100 c.c. solution. 

These figures indicate that if the solution is prepared in a flask 
the product will practically be of uniform strength. 

It is true the N. F. does not state whether a flask or evaporating 
dish should be employed. The result of the failure to specifically 
state that a flask or similar vessel be used is shown by the analyses 



358 Preservatives in Syrup of Iron Iodide. { Ab S j ^5* S£ m ' 

to yield preparations of indefinite strength. . If a large enough flask 
is not at hand, vessels which are deep should be employed, the object 
being to avoid too rapid evaporation of water, as the proper prepa- 
ration of the product requires several hours. 

In view of the above results the Committee on National Formu- 
lary should revise the wording of the directions for the preparation 
of Vleminckx's solution, and thus insure a uniform product. Of 
course if thought necessary a standard could be fixed for the prepa- 
ration and a method of assay appended. 

I would take this opportunity to acknowledge my indebtedness 
to my assistant, J. H. Wiener, Ph.C, for assistance rendered in the 
preparation and analyses of some of the samples. 



A NOTE ON THE VALUE OF PRESERVATIVES IN 
SYRUP OF IRON IODIDE. 1 

By George M. Beringer. 

In the U. S. P. 8th Revision, diluted hypophosphorous acid to 
the extent of 20 Cc. to 1000 Gm. has been added to this syrup as 
a preservative. Several of the foreign pharmacopoeias have used 
organic acids for the same purpose, the Austrian Pharmacopoeia 
directing 0.1 per cent, of citric acid, the Swiss Pharmacopoeia 0.05 
per cent, of citric acid, and the French Pharmacopoeia 0.1 per cent, 
tartaric acid. The German Pharmacopoeia, the British Pharma- 
copoeia, the Danish Pharmacopoeia, the Swedish Pharmacopoeia, and 
the Italian Pharmacopoeia do not direct any preservative, dependence 
being placed upon the use of sufficient sugar. 

In order to test out the relative value of these preservatives, 
six samples of syrup of iron iodide were prepared on October 15, 
1913. In all of these the official process and manipulation and 
percentage of iron salt and sugar were carefully followed. These 
samples were preserved in my laboratory and not exposed to direct 
sunlight for several months. On December 18th, their condition 
was observed and noted. Subsequently these samples were filed 
with Chairman Remington and preserved in his laboratory with 
the other pharmacopoeial samples until a few days ago, when I 
obtained them for observation of the further changes that had 



1 Read at the meeting of the New Jersey Pharmaceutical Association, 
Lake Hopatcong, June 17, 1914. 



Am AuoMi"t' Si? 111 '} Preservatives in Syrup of Iron Iodide. 359 

taken place. In the tabulation below the appearance on these two 
dates of each sample is noted: 

No. 1. — Proportions of the U. S. P. formula, but without any 
preservative. On December 18th this sample was slightly yellow. 
It is now of a pale green color and appears to be in perfect condition. 

No. 2. — U. S. P. 8th formula without any variation. On Decem- 
ber 18th this sample was very pale but perfectly clear. It was noted 
that the green color had gradually faded out and the sample was 
much lighter in color than when first prepared. This is in accord- 
ance with the observations on this formula that had been previously 
reported. 

This sample is now of a light yellow color and there is evidence 
of some change in the sugar, the change that we have commonly 
considered as caramelizing which takes place in the presence of 
hypophosphorous acid to a moderate extent. 

No. 3. — Proportions of the U. S. P. with the addition of 0.05 
per cent, of tartaric acid. This sample, on December 18th, had 
assumed a distinct yellow color. It has now faded until it is almost 
colorless. 

No. 4. — Proportions of the U. S. P. formula with 0.1 per cent, 
of tartaric acid. On December 18th this sample had retained the 
light green color about the same tint as when first prepared. It now 
shows no change and appears to be in perfect condition. 

No. 5. — Proportions of the U. S. P. formula with the addition of 
0.05 per cent, of citric acid. On December 18th this sample was of 
a very light green color and preservation appears to have been per- 
fect. It now shows no further change. 

No. 6. — Proportions of the U. S. P. formula with the addition 
of 0.1 per cent, of citric acid. On December 18th this sample had 
retained its original pale green color, and at this time preservation 
appears to have been perfect. 

Conclusions. — If syrup of iron iodide is carefully made and with 
the proper amount of sugar, no preservative whatever is needed. 
However,- to overcome the careless manipulation on the part of some 
druggists, it has been deemed advisable to add a preservative. 
Hypophosphorous acid has the advantage of a reducing value which 
is not possessed by the organic acid suggested for this purpose. It 
has, however, the disadvantage that in the strength directed it will 
act upon sugar in strong solutions and darken the syrup. This could 
be overcome by substituting glycerin for a portion of the sugar 
directed in the formula. 



360 



Petrolatum Liquidum, U. S. P. VI IL { K \*™£v&™' 



PETROLATUM LIQUIDUM, U. S. P. VIII (PARAFFINUM 
LIQUIDUM), WHITE MINERAL OIL. 

By S. L. Hilton. 

The U. S. P. VIII provides that this substance shall conform to 
the following description : 

A mixture of hydrocarbons, chiefly of the methane series, obtained 
by distilling off most ,of the higher and more volatile portions from 
petroleum and purifying the liquid residue. 

A colorless, or very slightly yellowish, oily, transparent liquid 
without odor or taste, but giving off, when heated, a faint odor of 
petroleum. 

Sp. gr. .870 to .940 at 25 C. Tests as to solubility, acid impuri- 
ties, fixed oils or fats, either animal or vegetable, and readily carbon- 
izable impurities. 

It is proposed for the U. S. P. IX to change the official title to 
Paraffinum Liquidum. This seems to be wise and in conformity 
to modern standards. The description, allowing a very slight yellow 
color, is a mistake, as there is no difficulty in obtaining a colorless oil 
except the oils of this kind that are produced in this country. The 
new requirement which requires that it shall be free from fluorescence 
is proper and not unnecessarily exacting. 

From a careful study of a number of samples of white mineral oil, 
obtained from various sources, the appended table shows that the 
official requirements can be met without much difficulty ; it is further 
demonstrated that an oil that is usually above the sp. gr. .870 will 
show more or less paraffin when subjected to a temperature of — 4 
C, yet in the table two samples, each of the sp. gr. of .875, remained 
perfectly clear after being subjected to this temperature for eight 
hours. It is therefore evident that in the process of purification 
chilling was not thorough or carried on for a sufficient length 
of time, and the final filtration was not performed at the same 
temperature. The desire to have as heavy oil as possible for internal 
administration, as recommended by Dr. Lane, of London, is no doubt 
accountable for such a large number of samples with a specific 
gravity lower than .875 becoming opaque or milky at this temperature. 

With proper manipulation and care an oil of the sp. gr. .8755 
should show no separation of paraffin on chilling. Some standard 
covering this point should be provided ; that is, a minimum specific 



A August," i9i? m '} Petrolatum Liquidum, U. S. P. VIII. 361 

gravity that will show no separation of paraffin when the oil is sub- 
jected to a temperature of at least o° C. 

None of the samples showed an admixture of fixed oils or fats, 
either animal or vegetable. The test is one that must be carefully 
applied, or an accident will follow. The neutralizing of the alkali 
with strong sulphuric acid, after digestion, is violent unless it is 
added very slowly. 

The results of the sulphuric acid test are most interesting, show- 
ing almost every shade of brown, and in several cases the only layer 
became opaque and colored and not conforming to the requirements 
of the pharmacopoeia or the standard as given in the British or 
German Pharmacopoeias. 

As to the internal administration of paraffin oil, a number of 
specialists of this city have used it for several years. The principal 
method followed by them is to administer from 15 to 50 Cc. at bed- 
time; in obstinate cases of constipation 15 Cc. administered about 
one hour before meals, so as to avoid interfering with the process 
of digestion. With these methods of administration good results 
have been produced. There are, however, many cases where com- 
plaints have been made that the oil will pass out of the intestinal 
tract involuntarily, very much to the discomfort of the patient, even 
when given in very small doses. This trouble seems to be more fre- 
quent with the administration of one of the popular brands of the 
market which shows a specific gravity of less than .860. To a certain 
extent this may account for the growing demand for heavier paraffin 
oils. 

Paraffin oils of a specific gravity of .880 or more are rather more 
difficult of administration than those of .870 to .875 ; they adhere to 
the mouth very closely, and to some are disagreeable and suggestive 
of castor oil. 

An oil aromatized or flavored with some essential oil or combina- 
tion of oils seems to be growing in demand. I submit ten samples, 
all of which, no doubt, to some would be agreeable. Personally, 
peppermint seems to be the most pleasant and agreeable ; cardamon 
a close second. No doubt, many would prefer spearmint, owing to 
the chewing-gum craze. 

The flavoring of paraffin oils must be done with care. From 5 to 
25 drops of an essential oil, according to which is used, will be found 
sufficient for 500 Cc. While this small amount may not give a pre- 
dominant odor, it must be remembered that the dose administered, 



362 



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An Au"u"t* SS**"} Physiological Characteristics of Acetylene. 363 

15 to 60 Cc., will be sufficient to give a fairly pronounced taste. The 
samples submitted contain in each 500 Cc. the following amounts of 
essential oils : Almond, 15 drops ; cloves, 10 drops ; anethol, 10 drops ; 
cinnamon, 5 drops ; peppermint, 15 drops ; spearmint, 15 drops ; sweet 
birch, 25 drops ; wintergreen, 25 drops ; and aromatic, using the oils 
constituting spirit aromaticus comp., 15 drops. 

Another interesting phase of the examination is the various 
prices charged for these paraffin oils, tlfose with fancy coined names 
commanding very much more than other oils on the open market, and 
all, or nearly all, coming from the same source and possibly the same 
importer. As has been pointed out by Mr. Wilbert, the better or fine 
grades come from Russia, hence the name Russian Mineral Oil; the 
American oil usually has a fluorescence, slightly yellow in color, and 
a more pronounced petroleum odor when heated. The best grades of 
Russian oil can be purchased for about 80 cents a gallon, while those 
with trade or coined names will cost from 40 to 60 cents a pint. 

The pharmacist should be, and is, able to supply physicians and his 
patients with an oil of high quality, reasonable in price, and should 
avail himself of the present opportunity. An oil of at least the sp. gr. 
.8750 that is colorless, tasteless, and free from fluorescence, that will 
not show more than a pale brown color with the sulphuric acid test, 
free from admixture with animal or vegetable oils, and remains clear 
when subjected to a temperature of o° C. for four hours, seems to be 
the oil most desired and, if demanded, can readily be obtained. 



THE PHYSIOLOGICAL CHARACTERISTICS OF ACETY- 
LENE, WITH RESPECT TO ITS USE IN MINING.* ■ 

By E. E. Smith, Ph.D., M.D. 

Like every other step in the progress of civilization, the use of 
acetylene involves certain readjustments of previous notions. In 
the art of illumination, these problems of adjustment have been 
particularly definite and impelling. Thus, the pine knot did not give 
way to the candle, probably, without anxious consideration of the 
danger of spattering, soot making, and extinction by drafts. Many 

* A paper read at a meeting of the International Acetylene Association, 
late in 1913, for a report of which the Quarterly is indebted to Secretary 
A. C. Morrison, 42d St., Building, New York. Reprinted from the School 
of Mines Quarterly, vol. xxxv., 1914, pp. 143-153. 



364 Physiological Characteristics of Acetylene. j A ^ u J g ° u s t' i P 9 H rm * 

years of careful study were needed to solve the last of the dangers 
involved in the use of kerosene, while the difficulties connected 
with illuminating gas and electricity are still with us. This paper 
will be limited to the problems of adjustment presented by the use of 
acetylene as an illuminant. 

This leads us at once to the inquiry, Is acetylene a direct poison? 
The answer is no. This question is asked with some seriousness, 
however, because, on the one hand, of the notoriously toxic action 
of common illuminating gas, due to the carbon monoxide which 
enters so largely into its composition, by reason of which the mind 
of the inquirer is already not only prepared to believe that acety- 
lene is poisonous, but, in fact, in some instances has that idea rigidly 
implanted there. It is further asked with seriousness, because, in 
the literature of the subject, -we find some views that it is poisonous. 
Early writers declared that it combined with the blood and had 
a marked poisonous effect, like carbon monoxide. 

Any gas, when it replaces air, if incapable of supporting respira- 
tion, is injurious and even fatal, not because it is poisonous but 
because it deprives the body of oxygen. Because of this, acetylene 
is capable of doing injury. If it accumulates in some small, unventi- 
lated space, like the cabin of a boat, it is entirely capable of shutting 
off the supply of air, of preventing respiration and hence causing 
harm and even death. It suffocates because it is incapable of 
supplying oxygen, without which man cannot live. 

When acting in this way, acetylene is not a direct poison ; it does 
not do anything to the body to injure it. It does harm only in- 
directly, by withholding air. The recognition, then, of injury by 
suffocation throws no light on our inquiry whether it is a direct 
poison. The presence of common illuminating gas in air, even 
to the amount of a fraction of a per cent., is distinctly injurious 
and may even be fatal, though such air contain an abundance of 
oxygen. The carbon monoxide contained in illuminating gas enters 
the blood through the lungs and attaches itself strongly to the color- 
ing matter of the blood, rendering it incapable of taking up the 
oxygen of air though the air contain oxygen in ample amount. Thus 
death supervenes not because the body is denied oxygen but because, 
through the fixation of the coloring matter of the blood, it has lost 
its capacity to use oxygen. Has acetylene this or any other directly 
poisonous action? Some early observers said it had. They found 
fixation of haemoglobin quite similar to that of carbon monoxide 



AD Augu"t' mT™' } Physiological Characteristics of Acetylene. 365 

and accordingly declared acetylene a poison. Moreover, it seemed 
to exercise the action of a direct poison on animals. 

This was ascertained before acetylene was regularly produced 
from carbide. The acetylene of that date was made by the incom- 
plete combustion of coal-gas, whence more or less carbon monoxide 
was present in the acetylene obtained, thus accounting for some 
degree of toxic action of the acetylene examined. Carbon monoxide 
is the poison of common illuminating gas. 

With the discovery of carbide and its use for the production of 
acetylene, all of this has been changed, it is now found that acety- 
lene from carbide does not contain carbon monoxide, that it does 
not have the property of fixing haemoglobin, and that it does not 
rob the blood of its capacity to take up oxygen from the air and 
carry it into the tissues. Hence the old allegation that acetylene 
is a poison because it deprives the blood of its oxygen-carrying 
capacity is no longer justified. 

Another poisonous product sometimes present in the acetylene 
made by the old combustion process was hydrocyanic acid. Never 
in large quantities, it yet is so toxic that we can fully appreciate its 
effect. It is not present in the carbide acetylene and so may be 
dismissed from consideration. Another charge that is no longer 
justified is that acetylene is a poison because of the presence of 
phosphine as an impurity. This forms when carbide is made from 
limestone containing phosphate, which is reduced by the action of 
the coke. The selection of limestone free from phosphate has prac- 
tically obviated this impurity and any poisonous effect of the acetylene 
consequent thereto. Indeed, the present day product may be said 
to avoid the pitfalls of impurities so that its effect is determined 
by the characteristics of acetylene itself. We may consider then 
whether acetylene, as such, is or is not a direct poison. 

My present observations have been directed to the inquiry whether 
it produced noticeable effect on human subjects when present in 
increasing amounts up to 2^2 per cent, during a period of 2^ hours. 
To this end, four men, including myself, were enclosed in a room 
of about 800 cu. ft. capacity ; at the beginning and four times 
subsequently at intervals of a half -hour, acetylene was liberated in 
the room bv throwing- 450 grams of carbide into an open tub of 
water, this corresponding to the liberation of 4 cu. ft. of acetylene 
each time; that is, 20 cu. ft. in all, 2 T / 2 per cent, of the capacity of the 
room. 



1 



366 Physiological Characteristics of Acetylene. { Am ( U g™ t r ' SJj™ 1 ' 

To eliminate, as far as possible, the mental effect of the environ- 
ment, the subjects were engaged in playing a game of cards. They 
were interrupted only long enough to take readings of their blood 
pressures, at half-hour intervals. The results of the experiment were 
quite negative. The game was continued throughout the period, 
excepting as noted. The blood pressure remained constant with 
one subject and was very slightly lowered from the inactivity with 
two, and absolutely no effect was noted that could be ascribed to any 
poisonous or other action of the acetylene. It was without effect. 

This same result has been obtained in experiments on animals. 
In such amounts as used in the above experiments there is no effect. 
Indeed, acetylene may be increased up to 20 per cent, and, if the 
mixture is so made as not to reduce the amount of oxygen, animals 
may be left in the atmosphere for some time, an hour or more, and 
will only become drowsy, from which they quickly recover when 
removed into ordinary air. 

With very large quantities, or with 20 per cent, admixtures act- 
ing for a longer time, the degree of drowsiness is increased. That 
is to say, the effect of acetylene in large doses is that of a narcotic, 
producing loss of consciousness in proportion to its degree of action. 
When this action is pushed to a fatal termination, the final effect is 
upon the breathing centre, inhibiting its action and so producing 
death. 

It thus appears that carbide acetylene is not poisonous in the 
sense that common illuminating gas is, and that in large quantities, 
acting for some time, it produces a narcotic action. In respect to 
its toxicity, it presents no problem of adjustment under ordinary 
conditions. It, of course, may not replace in large degree the atmos- 
phere we breathe, but otherwise no poisonous action need be antici- 
pated. 

A number of interesting problems are presented in connection 
with the use of the acetylene lamp as an illuminant in mines. I do 
not refer to those conditions where explosive gases are present, 
where protection from explosions is obtained through the use of the 
Davy lamp in some of its modifications, but to that large number 
of mines which are regularly illuminated by the naked flame. For 
this purpose, the miner's oil lamp has been used for many years, 
It is light in weight, but its illuminating capacity is strikingly low 
and, moreover, is obtained at the expense of a smoking-out process 
that is amazing. It is a tribute to the miner's endurance that in the 



^usust* fm™' } Physiological Characteristics of Acetylene. 367 

past he has accomplished so much under the conditions of poor 
illumination and soot-laden atmosphere which the use of the oil 
lamp has meant. The use of the miner's acetylene lamp affords an 
illumination that is wonderfully efficient and entirely soot- free. Its 
use raises some questions that we may answer at this time. Before 
considering these, let us look at some of the problems which the 
miner has to face, upon which the choice of an illuminant may have 
some bearing. Of first importance is the composition of the air which 
he breathes. 

For our present purpose we may regard the atmospheric air as 
a mixture of 21 parts of oxygen and 79 parts of inert gas, mostly 
nitrogen. It is the oxygen that supports life. The proportion of 
oxygen may be diminished to a certain extent without noticeable 
effect, especially if the difference is made up by inert nitrogen. Under 
these conditions a reduction to 14 per cent, produces little or no 
physiological effect. When the reduction reaches 12 per cent., 
there is apt to be slightly deeper breathing, while 10 per cent, is an 
amount distinctly below what is physiologically advisable. Seven 
per cent, may be regarded as the fatal point. It is an amount too 
small to support the life of animal or man for any considerable 
time. It must be kept in mind that these figures, 10 per cent, the 
physiological insufficiency and 7 per cent, the fatal point, are for 
oxygen with inert nitrogen, and without the admixture of poisonous 
gases. 

There is always present in atmospheric air a small amount of 
carbon dioxide gas, commonly known as carbonic acid. This amount 
is very small, ordinarily not over 5 parts in 10,000. It is a product 
of the combustion of organic matter and is present in air exhaled 
from the body in breathing. As we shall see later, it is also a con- 
stituent of mine gases and so is of particular interest to us. I will 
call attention to what happens when it is added to the air. 

To answer this question I have myself made direct observations. 
The apparatus employed was a closed cabinet, the inside measure- 
ments of which were approximately 67 x 30 x 69 in., having a capa- 
city of 80 cu. ft. It was provided with a sliding door. Into the 
top a pipe entered and connected with three " sprays," one in each 
third of the top. Through this system gases were introduced. There 
was a small sample tube, easily movable, so that gas was withdrawn 
from any position desired within the cabinet, which was connected 
outside with (a) an exhaust bottle for withdrawing residual air 



368 Physiological Characteristics of Acetylene. { A ^ U gu"t' SE**' 

from the tube; and (b) a gas-sampling tube. Collections were made 
over mercury and analysis was made over mercury in a Hempel 
apparatus. The cabinet was tightly built, but not sufficiently so 
to prevent escape of air sufficient to equalize the pressure without 
and within the cabinet when gas was introduced. A movable electric 
fan within the cabinet was adapted to produce motion of the air. 

When carbon dioxide was mixed with atmospheric air, it was 
noted that such mixture produced an increased rate of respiration, 
even when the proportion of carbon dioxide was small. Rabbits 
and guinea-pigs showed a marked increase when as much as 4 to 5 
per cent, of carbon dioxide was present. With increasing proportions 
respirations became deep and labored, frequently, as was observed 
in guinea-pigs, reaching a condition of diaphragmatic spasm. Loss 
of muscular power developed so that, with guinea-pigs, ability to 
support the body was lost when the carbon dioxide reached 20 to 25 
per cent. These symptoms developed irrespective of whether lamps 
were burnt in the same atmosphere. With rabbits, when lamps 
were burning, loss of muscular power appeared with the same pro- 
portion of carbon dioxide as with guinea-pigs, but in a single obser- 
vation made without lamps, the loss of power appeared when the 
carbon dioxide had reached 36 per cent. No effort was made to 
determine the percentage of carbon dioxide that would produce death, 
as it was believed that the proportion producing loss of muscular 
power represented the limit of possible tolerance. It may be noted, 
however, that in the experiment carried to 36 per cent, carbon dioxide, 
the rabbit quickly recovered, two guinea-pigs recovered somewhat 
slowly, and one guinea-pig died, when the animals were removed 
into fresh air. Thus it appears that even with guinea-pigs, the fatal 
carbon dioxide proportion is not much if any below 36 per cent, 
while the carbon dioxide warning point is not above 4 to 5 per cent., 

To test the effect of carbon dioxide on man, io J / 2 cu. ft. of carbon 
dioxide were passed into the cabinet, when a young man entered, the 
door being opened for that purpose and quickly closed. After 
entering, the fan was started. The rate of respiration at once rose 
from 18 to 48, being deeper and labored. He almost immediately 
complained of feeling dizzy. At the end of 2^ min. there was a 
feeling of impending loss of consciousness. A sample of the air 
mixture was at once taken and at the end of 3 min. the man came 
out. His respiration quickly returned to normal, but his face was 
flushed and he complained for several hours of a slight frontal 



AD August im. m ' } Physiological Characteristics of Acetylene. 369 

headache. Analysis of the sample showed 7 per cent, of carbon 
dioxide. The experiment indicated that with man the warning point 
is reached below 7 per cent, of carbon dioxide. 

Such experiments lead to the following general conclusions re- 
garding the physiological effects of increasing proportions of carbon 
dioxide. There is increase in the rate of breathing which, with 
3 per cent, dioxide, has become so marked that it gives unquestioned 
warning to the subject that some unusual condition of the air is 
rendering it unsuited for breathing. We may call this the physio- 
logical warning point for carbon dioxide. When the concentration 
reaches 8 to 10 per cent., the breathing is not only rapid but has 
become very labored, a condition termed dyspnea. Beyond 15 per 
cent., further concentration, instead of increasing respirations, de- 
creases them and the animal becomes narcotized, quite as though 
a substance like chloroform had been administered. At a concen- 
tration beyond 35 per cent, the narcosis becomes fatal. 

I have gone into the influence of oxygen decrease and of carbon 
dioxide increase on breathing and on life because these are condi- 
tions that may be presented by the air in mines. Moreover, the oil 
lamp has been relied upon to indicate to the miner whether or not 
the mine air is fit to breathe, air that sustains the flame being regarded 
as safe and air that extinguishes the flame as unsafe to breathe. 

The disadvantages of the oil lamp are all too apparent. Its dingy 
light limits the working capacity of the miner, due to poor illumina- 
tion. Aside from working capacity, the miner is not so well able 
to see the elements of danger presented by weakness in overhanging 
strata or structures. An even greater disadvantage is the production 
of soot by the flame. This both adds to the personal discomfort, 
already great, and also to the danger of dust explosions by addition 
of the soot to the dust-laden atmosphere. These conditions render 
an illuminant that is brilliant and soot-free a very great advantage. 
The acetylene lamp supplies such an illuminant in an admirable 
manner. In connection with its use it is desirable to determine its 
relation to composition of mine air, so that the miner may know in 
what way and to what extent it replaces the oil lamp as an index 
of safety. That is to say, we have here a problem of adjust- 
ment to which it is important to give a correct and definite answer. 

First, then, let us consider the variations in composition that 
may be presented by mine air. Because of the limitations of access 
of outside air and especially because of the formation of gases in 



370 Physiological Characteristics of Acetylene. { Au i U gu"t' 



Pharm. 
1914. 



mines, mine air may present a considerable departure from the 
composition of outside air. 

All ordinary foreign gases were known to the early miners as 
" damps/' from the German damf, meaning vapor, the specific desig- 
nation being indicated by an individual prefix. Thus, the gas charac- 
terized by its tendency to extinguish the flame was called black- 
damp, or, since it tends to produce suffocation, choke-damp; the 
damp producing increased brilliancy of light, white-damp ; that with 
a marked stink, stink-damp ; that which readily took fire, fire-damp ; 
the gas resulting from burning or explosion, after-damp, etc. These 
names were applied long before the composition of the respective 
gases was known. In consequence of the indefinite basis of the 
classification, an individual name was in many instances applied to 
mixtures that presented wide variation in composition. 

Black-damp, on chemical analysis, has ordinarily proved to be 
a mixture of carbon dioxide and nitrogen, the proportion of carbon 
dioxide varying from very little up to 15 per cent, or perhaps excep- 
tionally 20 per cent. As it is always mixed with more or less air, 
a corresponding amount of oxygen is present. Other gases, such as 
methane (fire-damp), carbon monoxide (white-damp), hydrogen- 
sulphide (stink-damp), also water vapor, may be present in greater 
or less amount. 

We may well ask, then, what the name black-damp indicates. 
Does it mean carbon dioxide, which is the characteristic constituent ; 
does it mean the carbon dioxide-nitrogen mixture; is it the carbon 
dioxide-nitrogen-air mixture; or is it the combination of any of these 
with other gases that are present in the mine air? Unfortunately, 
there has been no unanimity of usage in regard to this term, it having 
been used by different writers in almost every one of the above pos- 
sible meanings. 

If we were to establish anew the definition of the term, it would 
be doubtless wise to adopt a scientific meaning. As the matter stands, 
our meaning should be decided by priority, which is that black-damp 
is not simply carbon dioxide but rather a mixture of that with nitro- 
gen in varying proportions, but we must not forget the different 
usages of individual authors. 

Our problem is : How does the admixture of black-damp modify 
the respirability of mine air and how is this indicated by the oil and 
acetylene flames? It requires no facts other than those now before 
us id appreciate that it affects respirability in two ways. It dimin- 



AD Auiu U 8t' i9 h i4 rm '} Physiological Characteristics of Acetylene. 371 

ishes the proportion of oxygen which, if reduced to 10 per cent., 
would be unphysiological and to 7 per cent., fatal ; and it increases 
carbon dioxide which, when present to the amount of 3 to 4 per cent., 
would produce marked increase in the rate of breathing. 

As to when the change in composition, especially the carbon 
dioxide increase, is indicated by the particular flames, has been the 
subject of personal experimental observations. The cabinet employed 
in the experiment previously described was used. In the earlier 
experiments with carbon dioxide, this gas was fed into the cabinet 
without previous admixture with air ; in the later ones both air and 
carbon dioxide were fed into the cabinet through meters, entering 
the cabinet through a common tube. Thus they were well mixed 
and the rate of flow of each was regulated. Early experiments indi- 
cated that various factors influenced the extinction point, both for 
the oil and acetylene lamp. Let me relate what these factors were 
and how they exercised their influence. 

A. Actylene Gas Pressure. — From the outset it was observed 
that the pressure under which the acetylene gas was fed through 
the burner exercised a marked influence upon the extinction point. 
That is to say, with a series of lamps in which the acetylene gas 
pressure varied, as indicated by the character of the flame, it was 
not difficult, in a mixture of increasing proportion of carbon dioxide, 
to foretell the order in which the lamps would be extinguished, the 
lamps with higher acetylene pressure going out first. Indeed, it 
was frequently observed, where the escape of gas from the burner 
was under such slight pressure as not to give direction to the flame, 
that the extinction point would be very much higher than was 
observed with the ordinary burning flame. Care was therefore 
exercised to make our observations on lamps in which the gas 
production showed a normal amount of pressure. 

B. Air Movement. — When there was no movement of air, except- 
ing such as resulted from the convection currents produced by the 
lamps and by the introduction of the gas mixture, the extinction 
points were: for the acetylene lamps, 23 to 25 per cent, carbon 
dioxide; for the oil lamps, 12 to 14 per cent, carbon dioxide. With 
the production of a gentle movement of the air by fanning against 
the side of the cabinet, the extinction points were appreciably 
affected, being lowered in the case of the acetylene lamps to 22 to 17 
per cent, carbon dioxide ; in the case of oil lamps to 12 to 10 per cent, 
carbon dioxide. 



372 Physiological Characteristics of Acetylene. { Al A U gS' mi""" 

With the production of a strong movement of the air, by direct 
fanning of the lamps, in two experiments the acetylene lamps were 
extinguished when the air contained 9.4 per cent, and 9,9 per cent, 
carbon dioxide, respectively, while the oil lamps were extinguished 
by the same breeze in atmospheric air. 

'The movement of the lamps worn on the heads of the miners 
would produce, in quiet air, the effects that result from a breeze with 
the lamps stationary. We may conclude, therefore, that in the case 
of the acetylene lamp the extinction point is lower than 25 per cent., 
in proportion to the rapidity of motion; and with the oil lamps, 
correspondingly lower than 14 per cent. 

C. Oxygen Proportion. — In the experiments mentioned, the oxy- 
gen was reduced only moderately by the admixture of the carbon 
dioxide in the form of pure gas. Undoubtedly, such reduction tends 
to lower the carbon dioxide extinction point. The effect, however, 
is only moderate, since the oxygen in all experiments was distinctly 
more than would sustain the flame if the specific effect of the carbon 
dioxide were neglected. 

When the admixture of carbon dioxide is in the form of black- 
damp, however, the question of the oxygen proportion becomes an 
important factor for consideration. In these preliminary investiga- 
tions, we were not able to study the effect of black-damp, since with 
the use of so large a cabinet, the quantity of nitrogen required would 
be much greater than it was practical to obtain. 

D. Humidity. — In a number of experiments, water vapor was 
introduced into the gas mixture by blowing over the surface of water 
within the cabinet. In this way, the humidity was raised from 
approximately 35 to 65 or 80. Any effect upon flame extinction by 
carbon dioxide that may have resulted was within the limits of varia- 
tion from the other factors considered. The conclusion is therefore 
reached that humidity affects the proportion of carbon dioxide 
required to produce flame extinction only within relatively narrow 
limits. 

Comparing now the effects of carbon dioxide increase on flame 
extinction and respiration, we note that the first effect is a physio- 
logical one, when the proportion reaches 3 to 4 per cent., there being 
an increase in the respiratory rate that is entirely adequate to warn 
persons of the atmospheric condition. Flame extinction occurs with 
oil at 13 per cent, and acetylene at 26 per cent, in still atmosphere, 
but at 10 per cent, and 17 per cent, with moderate motion. With 



An Aimi U st' i9i4 im '] Physiological Characteristics of Acetylene. 373 

either lamp the extinction point is too high above the physiological 
warning point to make it of value to the miner. The conditions will 
have been recognized before the extinction point is reached. Should, 
however, the physiological warning be unheeded, flame extinction 
will occur, first with the oil and then with the acetylene flame, with 
either in ample time to prevent loss of life. The margin of safety, 
though greater with the oil lamp, is adequate with the acetylene. 

In considering the influence of oxygen decrease on flame extinc- 
tion, I shall make use of observations made by Chester S. Heath, 
under experimental conditions different from those I have described. 

He finds that with moderate motion an oil flame is extinguished 
when the oxygen is reduced to 16.5 per cent. ; in still air to 16.2 per 
cent. With acetylene, at moderate motion, extinction occurred at 
12.6 per cent, and was dimmed in still air of the same composition, 
being extinguished in still air at 1 1.5 per cent. It thus appears that 
the oil flame is extinguished with considerably less reduction of 
oxygen than the acetylene, but that the latter is extinguished before 
the reduction is fatal to man, which is at 7 per cent. Moreover, 
in actual mining conditions, where the lamp is worn on the head, there 
will be sufficient motion; hence extinction will occur at a point 
somewhere above that observed with the experimental conditions. 

Finally, it is not to be forgotten that the condition of extreme 
oxygen reduction without carbon dioxide increase, which was present 
in the experimental observations, is not encountered in actual mine 
air. The specific action of carbon dioxide admixture, that will be 
found in such conditions, will add its effect to the oxygen decrease 
and bring about the extinction of an acetylene flame at a point which 
is still further removed from unphysiological atmospheric conditions, 
and hence afford an increased margin of safety. 

The miner, then, may conclude that a given admixture of black- 
damp and air in the absence of other foreign gases will support 
life: (1) if it does not extinguish flame; (2) if it does not produce 
markedly increased respiration. Any atmosphere which does not 
give these warnings is respirable, though not necessarily desirable 
for continuous respiration. It does, however, give warning either 
physiological, or by the flame of acetylene as well as oil, that is 
adequate to prevent loss of life. 



/ 



374 65th Annual Session of A. M. A. { Am ^ u l°Zt m a 4 rm ' 

THE 65TH ANNUAL SESSION OF THE AMERICAN 
MEDICAL ASSOCIATION. 

By M. I. Wilbert, Washington, D. C. 

The 191 3 meeting of the American Medical Association was held 
in Atlantic City, June 22-26, and was attended by 3958 members 
who took the time and trouble to register. The registration this 
year is reported to have been considerably larger than that of any of 
the previous sessions of the Association in Atlantic City. The work 
of the House of Delegates and its committees and the proceedings 
of the several sections of the Association are reported at length in 
the Journal of the American Medical Association for July 4, 1914, 
vol. 63, pp. 73-130. The scientific papers, because of the restrictions 
imposed by the House of Delegates at the Minneapolis meeting, were 
fewer in number than in former years, but the subject matter dis- 
cussed was correspondingly good, the programs for the several 
sections being generally well carried out. 

The Section on Pharmacology and Therapeutics had, as usual, 
a program containing many papers of pharmaceutical interest. Dele- 
gates from the American Pharmaceutical Association were recog- 
nized, and Prof. Joseph P. Remington, the chairman of this dele- 
gation, in extending the felicitations of the organization he repre- 
sented, said: 

" The American Pharmaceutical Association brings greetings to 
the American Medical Association. It is meet and proper that two 
national bodies should exchange greetings, for, however they may 
differ in function and scope, they are united in principle in the one 
great object of promoting the health of the nation in combating 
disease. 

" It is gratifying to know that the Pharmacopoeia is practically 
completed, so far as the bulk of the work is concerned. The printing 
of the Appendix, with the Tables, Reagents, and Volumetric Solu- 
tions, will be sent to the printer this week, for this part of the book 
must be printed first, in order that members may have it for refer- 
ence in checking up the text of the book. 

" During the past year a number of older remedies have been 
deleted and new remedies admitted. A Committee on Scope which 
reports upon proposed admissions and deletions have finished their 
work, but there are still a few questions which can be settled after 



Af Augu U s t,' 191™'} 65th Annual Session of A. M. A. 375 

the printing is started. One of these questions is the form of so- 
called bichloride tablets. As is well known, the enormous use of 
these tablets is a menace to the future growth and prosperity of the 
nation. The Pharmacopceia cannot check the use of these tablets, 
but it can at least direct the form for their use which will prevent acci- 
dent so far as possible through swallowing the tablets or their solution. 

" The American Pharmaceutical Association, during the past 
year, has used its influence in every possible way in controlling or 
limiting the use of habit- forming drugs by national and State legis- 
lation. Committees have been formed from the membership who 
are working to stamp out this evil. 

" The body which I have the honor to represent asks the assist- 
ance of your body to aid in framing wise laws which will make it 
difficult for dopesters to continue their habits, and by limiting the 
use of these drugs to prescriptions by properly educated physicians, 
who are earnestly trying to curtail the evil. 

" In educational matters Pharmacy has progressed in the direc- 
tion of raising the standard of education of those entering Pharmacy, 
and enlarging the curriculum in the colleges. May we not hope 
that Medicine and Pharmacy will be more closely linked in the 
future, and that crimination and recrimination will cease, or take 
the form of constructive criticism, with the intention of remedying 
the evils and correcting abuses, and will be actuated by harmony 
between the two professions." 

Referring more particularly to the probable scope of the U. S. P. 
IX, the following table represents the status of that book at the 
present time: 



Number of articles in text of U. S. P. VIII 95$ 

U. S. P. VIII articles dismissed from U. S. P. IX list 237 

Number of articles retained from U. S. P. VIII , 721 

Number of new articles admitted to U. S. P. IX 67 

Total number of articles in tentative list of U. S. P. IX 788 



On motion of Dr. Murray Gait Motter, of Washington, D. C, 
the Section on Pharmacology and Therapeutics of the American 
Medical Association adopted the following resolution, which was 
referred to the House of Delegates, endorsed by that body, and thus 
officially recognized as the opinion of the American Medical Associa- 
tion : 



376 65th Annual Session of A. M. A. { Am x U gu D 8t" wm™ 1 " 

" Whereas, The Pharmacopoeia of the United States of America 
should be, above all, a book designed to protect the public health 
and prevent the exploitation of the sick and afflicted for profit ; now, 
therefore, be it 

"Resolved, That the members of the Section on Pharmacology 
and Therapeutics of the American Medical Association request the 
House of Delegates to urge upon the Revision Committee to make 
official in the Pharmacopoeia of the United States 'corrosive mer- 
curic chloride pastilles,' so that physicians may not be compelled 
to prescribe this remedy under a proprietary name. Be it further 

"Resolved, That this section endorse the form and description 
of corrosive mercuric chloride pastilles as described in the German 
Pharmacopoeia, namely, of cylindrical shape, twice as long as thick, 
wrapped individually in paper bearing the name of the medicament, 
' corrosive mercuric chloride pastilles,' and the word ' poison ' in 
suitable and striking letters. Be it further 

"Resolved, That a copy of this resolution be forwarded by the 
Secretary of the American Medical Association to the President 
and to each of the officers of the United States Pharmacopceial Con- 
vention, and also to the Chairman and to each member of the Com- 
mittee of Revision of the Pharmacopoeia of the United States." 

Of the many papers presented in the Section on Pharmacology 
and Therapeutics, the following contributions were of more imme- 
diate interest to pharmacy : 

Dr. John F. Anderson, the chairman of the Section on Pharma- 
cology and Therapeutics, in his address discussed some unhealthy 
tendencies in therapeutics and referred more particularly to the ill- 
advised use of certain biologic products, such as the Friedmann vac- 
cine for tuberculosis and crotalin in the treatment of epilepsy. In 
summing up this paper he suggested that, while advances in therapeu- 
tics are necessary and clinical trials must be made, these trials should 
be with adequate controls of otherwise treated cases and under cir- 
cumstances in which every stage can be watched and the various clini- 
cal and laboratory observations be made a matter of unbiased record, 
and the best interests of the patients thus safeguarded. It is difficult 
to secure these conditions outside of a well-equipped hospital. Until 
a new method of treatment has received abundant confirmation of this 
sort it is unjust — to use no stronger word — to apply it promiscuously 
to patients who are not under constant observation and are not 
amenable to instant emergency relief. 



Am AugS;wM! m '} 6 5 th A nnual Session of A. M. A. 377 

In a paper on " The Medical Treatment of Chronic Intestinal 
Stasis," W. A. Bastedo, of New York, discussed the uses and limi- 
tations of many of the aperients and cathartics. In commenting on 
the now widely used paraffin oil, he called attention to a series of ten 
samples not one of which complied strictly with the requirements 
of the Pharmacopoeia, and also stated that in writing prescriptions for 
paraffin oil or liquid petrolatum it is unfortunately true that it is prac- 
tically necessary to specify some established brand, as the material 
supplied in retail drug stores very seldom, if ever, complies with the 
requirements of the Pharmacopoeia or is of an otherwise satisfactory 
nature. 

In a paper on active immunization in diphtheria by toxin-anti- 
toxin mixtures, William H. Park, of New York, reported on recent 
progress in the prophylaxis of diphtheria and reviewed the present- 
day knowledge regarding immunization and the possible recognition 
of immunization by skin reaction. 

In a paper on the use of diphtheria antitoxin in the treatment of 
diphtheria, Samuel S. Woody, of Philadelphia, recommended the 
administration of much larger doses than are used at present, and also 
asserted that the number of antitoxin units to be administered should 
be in keeping with the stage of the disease. He also stated that as a 
prophylactic diphtheria antitoxin was uncertain and in a great meas- 
ure unsatisfactory in its results, and that to be efficacious in the treat- 
ment of diphtheria, antitoxin must be given at the earliest possible, 
moment and in large doses. 

In addition to the resolution endorsing the inclusion of pastilles 
of corrosive mercuric chloride in the Pharmacopoeia of the United 
States, the House of Delegates also adopted the following recom- 
mendation of pharmaceutical interest suggested by the Council on 
Medical Education and endorsed by the reference committee: 

" Your committee also recommends that the Council be instructed 
to urge all medical colleges to adopt the nomenclature of thte Pharma- 
copoeia of 1910, and to use the metric system in their teaching." 

The scientific exhibit was of unusual interest, and the work dis- 
played was not alone excellent, but much of it was of immediate prac- 
tical value to the profession. The commercial exhibit attracted con- 
siderable attention and was unusually free from objectionable 
features in the way of proprietary and semi-proprietary prepara- 
tions not recognized by the Council on Pharmacy and Chemistry. 

The officials for the Section on Pharmacology and Therapeutics 



378 



Book Reviews. 



J Am. Jour. Pharm. 
t August, 1914. 



for the coming year are : Chairman, R. A. Hatcher ; vice-chairman, 
J. Ray Arneil ; secretary, M'. I. Wilbert ; delegate, John F. Anderson, 
and alternate, Ray L. Wilbur. 

At the opening meeting of the Association on Tuesday morning 
Dr. Victor C. Vaughan, of Ann Arbor, Mich., was installed as presi- 
dent, and at the concluding session of the House of Delegates on 
Thursday afternoon Dr. Wm. L. Rodman, of Philadelphia, was 
selected as the president-elect and San Francisco chosen as the place 
of meeting for 1915. 



BOOK REVIEWS. 

Digest of Comments on the Pharmacopoeia of the United 
States of America and on the National Formulary for the 
Year Ending December 31, 1912. By M. I. Wilbert and M. G. 
Motter. 

One hardly realizes the vast amount of writing done annually in 
reference to pharmacopceial matters until one peruses the above 
useful compilation and the several that preceded it. 

We do not say that Charles Rice " builded better than he knew," 
because he knew many things, if all we have learned of him is 
true, but he certainly built wisely and with the foresight possessed 
by a great mind when he suggested and carried out the idea of com- 
pilation and classification of critical references anent matters pharma- 
ceutical. That we live in a day and under a form of government that 
sees its way clear to carry this idea to fuller fruition augurs well for 
pharmacy in this country. Jofin K. Thum. 

Annual Report of the Investigations Carried Out under 
the Supervision of the Therapeutic Research Committee of 
the Council on Pharmacy and Chemistry of the American 
Medical Association, Volume II, 1913. 

This small volume of 11 1 pages embodies the results of some 
practical research work that is bound to have an influence for good 
on medicine and pharmacy. Both physicians and pharmacists would 
do well to purchase this little volume, which can be obtained for 
a small sum, for it will put them in possession of some positive knowl- 
edge on the possibilities and limitations of some well-known drugs. 
While it may be true, as is sometimes said, that medicine is not an 



Am AuKu U J; wu m } Philadelphia College of Pharmacy. 379 

" exact science," yet if it is ever to be raised from the slough of 
empiricism, work of this kind must be done and persistently promul- 
gated among the members of the professions. 

John K. Thum. 



PHILADELPHIA COLLEGE OF PHARMACY. 

Quarterly Meeting. 

The quarterly meeting of the Philadelphia College of Pharmacy 
was held June 29, 1914, at 4 p.m., in the Library; the President, 
Howard B. French, in the chair. • Fifteen members were present. 
The minutes of the annual meeting, held March 30, 1914, were read 
and approved. 

The minutes of the Board of Trustees for March, April, and 
May were read by the Registrar, J. S. Beetem, and approved. The 
report of the Committee on Necrology was read by the Chairman, 
and referred for publication in the American Journal of 
Pharmacy. 

Professor Stroup reported verbally for the delegates to the Penn- 
sylvania Pharmaceutical Association. The attendance was some- 
what smaller than usual. The reception of delegates from other 
organizations and reports of delegates to other bodies were the 
features of the first day's session. A large number of papers were, 
as usual, presented, the one on " Bacterial Vaccines and Serums,'' by 
Dr. A. P. Hitchens, being most interesting. The report of the 
Legislative Committee and the report of the Secretary of the State 
Pharmaceutical Board were also presented. The president, R. H. 
Lackey, made a number of recommendations which, after being re- 
ferred to a special committee, were adopted. The Association elected 
the former secretary, E. F. FlefYner, president, and David J. Reese, 
secretary. The next meeting is to be held at Forest Park, Pike 
County. 

The delegates to the Delaware Pharmaceutical Association re- 
ported verbally by its chairman, Dr. A. W. Miller. The meeting 
was held at Hotel Du Pont, Wilmington, on June 4th. The reports 
of the officers and committees occupied the morning session. The 
meeting was not a very large one, but a very harmonious one. Your 
delegate was accorded a cordial welcome, who urged upon the 
members their help to influence congressional action in securing a 



380 Philadelphia College of Pharmacy. { k \*^*imA^* 

site for the statue to Professor Procter in front of the Smithsonian 
Institution. 

The delegates to the New Jersey Pharmaceutical Association re- 
ported through the chairman, George M. Beringer. The 44th annual 
meeting was held at Hotel Breslin, Lake Hopatcong, June 16th to 
19th. The absence of other members of the delegation, owing to the 
commencement exercises of the College occurring at the same time, 
was very much regretted. The meeting was one of the largest 
attended and most interesting sessions ever held. The sessions were 
well attended, and under the able executive the business was thor- 
oughly yet expeditiously considered. Legislative matters were again 
one of the principal topics considered and the incoming Legislative 
Committee was instructed to have the proposed new pharmacy 
law, with a prerequisite clause, again presented to the next 
Legislature, and to use their best endeavors to have this bill 
enacted. The Committee on Papers and Queries presented an 
unusually interesting report. About twenty papers were read and 
discussed. A number of these were contributions from the members 
of this College. The subjects covered a wide range: commercial, 
educational, legal, scientific, and practical pharmaceutical questions 
were treated in these papers. Of no less interest were the discus- 
sions they provoked. The internal alfairs and finances of the Asso- 
ciation were subjects for earnest consideration. The President, in 
his annual address, advocated an increase in the dues in order to 
avoid a deficiency. Mr. John C. Gallagher, of Jersey City, was 
elected president, and Mr. G. M. Hays Deemer, of Atlantic City, 
was elected vice-president. The entertainments provided by the 
Local Committee and Travelling Men's Auxiliary were good and 
sufficient for the occasion without infracting upon the time needed 
for business. 

Professor Kraemer presented the following resolution referring 
to a celebration of the fiftieth anniversary of the founding of the 
Alumni Association : 

"As the session of 1914-15 will mark fifty years since the 
Alumni Association of the Philadelphia College of Pharmacy was 
established, and as the founders rendered yeoman service in the 
development of the educational facilities of the College, Resolved, 
That the College recognize this interest in her former students 
and arrange for a fitting celebration to commemorate this mile- 
stone in the history of the Association." 

The reading of the paper caused considerable discussion. Mr. 



Al Aiigu"t' SiT"') Philadelphia College of Pharmacy. 



38i 



French said that the Alumni Association had been foremost in all 
the advances the College had made, either as the originator or sup- 
porter of these advanced movements. The discussion was further 
participated in by Messrs. Beringer, Kraemer, Foley, French, Miller, 
and Stroup, when Mr. Beringer moved that a joint committee of the 
Board of Trustees and the Alumni Association be appointed to 
consider the matter. Adopted. 

Professor Kraemer presented a framed receipt for two hundred 
dollars, contributed by the Class of 1889 for the Centenary Fund now 
in process of collection. On motion, it was voted to place it in the 
Library. 

Professor Kraemer referred to the work which had been done 
during the past fifteen years, prior to the establishment of the present 
course in Bacteriology, and requested that a succinct account of the 
work be compiled from the reports of the Committees on Instruction 
and Examination. 

Mr. Beringer, in commenting on the paper just read, said he 
wanted to call particular attention to the advances the College has 
made in its courses of instruction. There should be still further 
advances made. We should have post-graduate courses. No other 
college is giving the advanced courses that we are giving, especially 
in Pharmacognosy. More publicity should be given to the instruc- 
tion given in the College. Our third-year class should be augmented 
from graduates of other institutions who are receiving less than we 
are giving. 

The President made the following appointments : 

Committee on Nominations: W. A. Rumsey, E. F. Cook, W. L. 

Cliffe, Otto Kraus, John K. Thum. 

Committee on Necrology : Henry Kraemer, Joseph W. England, 

C. A. Weidemann. 

C. A. Weidemann, M.D., 

Recording Secretary. 



ABSTRACTS FROM MINUTES OF THE BOARD OF 
TRUSTEES. 

March 3, 1914- — Thirteen members present. 
Committee on Property reported that a lunch room had been 
opened, that the lunches furnished were of good quality, and that 



382 Philadelphia College of Pharmacy. \ A \^i,vdu. m ' 

the number of student patrons was greater than had been expected. 
The caterer expressed his satisfaction at the results of the undertak- 
ing, and it was regarded a success. The committee suggested the 
advisability of larger accommodations for the next session. The 
committee also reported complaints having been made concerning 
students smoking throughout the building, and advocated the en- 
forcement of more stringent rules governing this practice, confining 
smoking to the cemented portions of the first floor and basement. 

Committee on Library reported 398 books accessioned during the 
month, making a total of 6676 books ready for cataloging. Two 
hundred and forty-one persons had used the Library. 

Committee on Examinations presented the results of the recent 
examinations held at the end of the first semester for the classes 
of the first, second, and third years. 

Committee on By-laws proposed several amendments : To amend 
Article 8, Section 3. To amend Article 11, making same Article 12, 
and to introduce a new Article on Scholarships and Fellowships, as 
Article 11. Action was deferred until the next meeting. 

Committee on Athletics presented a communication from the stu- 
dents representing the track team. The committee felt that the mat- 
ter of athletics was one to be assumed by the Alumni Association and 
to be under their control and support. The subject was referred to 
the President of the Alumni Association. 

Committee on Membership reported favorably on the application 
of Miss Agnes Duvoisin ; a ballot was taken and she was unani- 
mously elected to active membership. 

April 7, 1914. — Thirteen members present. A communication 
was received from the Recording Secretary of the College, announc- 
ing the election of officers for the ensuing year and three Trustees for 
three years (see this Journal, p. 229). 

Nominations for officers of the Board being in order, George M'. 
Beringer was elected chairman ; Walter A. Rumsey, vice-chairman, 
and Jacob S. Beetem, registrar. 

The Chairman read a communication from the stafY of the 
" Graduate " 1913, offering to present a loving cup to be awarded 
to the first-year class 1914, and competed for thereafter under the 
rules governing the award of the President's Cup. On motion the 
offer was accepted and the appreciation of the Board expressed. 

Dr. A. W. Miller read a communication from Professor Ernest 
Gilg acknowledging receipt of his Certificate of Honorary Member- 



AD Au J g .r s t; 1914™' } Philadelphia College of Pharmacy. 



383 



ship, for which he expressed appreciation and offered the College a 
set of his books. The offer was accepted with the thanks of the 
Board. 

The Chairman announced the Standing Committees for the ensu- 
ing year, as follows : Property, Howard B. French, chairman ; 
Library, Samuel P. Sadtler, chairman ; Museum and Herbarium, 
O. W. Osterlund, chairman ; Finance, Howard B. French, chairman ; 
Supplies, H, K. Mulford, chairman; Accounts and Audits, C. A. 
Weidemann, chairman; Instruction, George M. Beringer, chairman; 
Scholarships, Joseph P. Remington, chairman; Examinations, 
William L. Cliff e, chairman ; Theses, Joseph W. England, chairman ; 
Discipline, Howard B. French, chairman; Announcement, Samuel 
P. Sadtler, chairman ; Commencement, Walter A. Rumsey, chairman ; 
Alumni, Joseph W. England, chairman; Appropriations, composed of 
chairmen of all committees empowered to make expenditures, also 
the chairman of the Board of Trustees, the chairman of the Com- 
mittee on Finance, and the Treasurer. 

Mr. French presented souvenirs, consisting of invitations, pro- 
grams, menus, advertisements, etc., relating to past affairs of the 
College. These were of historic interest and were referred to the 
Historical Committee. 

Professor Remington referred to the Panama Exhibition in 191 5, 
expressing the thought that it would be to the advantage of the 
College to exhibit a line of official and N. F. preparations, together 
with historical matter, and suggested that a committee be appointed 
to make arrangements and that the College make an early appli- 
cation for space. On motion it was voted that a committee of five 
be appointed. 

April 21, 1914. — Eleven members were present. 

Committee on Examinations reported favorably on the appli- 
cation of Prof. Edwin Leigh Newcomb, P.D., for the degree of 
Master in Pharmacy in course, all the requirements having been 
complied with. A ballot was ordered and the applicant was unani- 
mously elected to receive the degree at the next commencement. 

Committee on Instruction reported that they had held a number 
of meetings to consider the annual reports from the Faculty. Ab- 
stracts from these reports are as follows : 

Department of Pharmacy: The record of attendance as now made 
obligatory has been of special value. The extra lectures on pharma- 
ceutical subjects have been attended by a much larger number of 



384 Philadelphia College of Pharmacy. {^^S* Su" ' 

students than heretofore ; the increased time given to this department 
has permitted considerable additional instruction in Operative 
Pharmacy. It is thought desirable that this department be fur- 
nished with a lantern for illustrating lectures on prescriptions, etc. 
Numerous slides have been accumulated, and these are used to 
advantage, but they are not as effective as the projection of the 
actual prescription. 

The course in Commercial Training has been greatly increased, 
and the former indifference of the students has given way to eager- 
ness to absorb information. 

The instructor in Latin reports that his work has been satisfactory. 

Department of Chemistry: Professor Sadtler reports upon the 
work of the second- and third-year classes. By the lengthening of 
the College year, and the increase in the hours of instruction, a more 
extended course of instruction is given. In addition to the course 
of public lectures that have been given in recent years to the third- 
year classes, it is thought that a series of lectures for the second- 
year class could be introduced to considerable advantage. As the 
instruction to the second-year class covers many of the commercial 
chemicals, it would seem that a series of lectures bearing upon that 
subject would be especially beneficial. 

Department of Materia Medica: Increased attention has been 
given to the physiological assaying of drugs with good results. 

Department of Botany and Pharmacognosy : Advanced methods 
have been used. With each laboratory lesson a mimeographed outline 
of the work is given the students, printed on sheets of uniform size 
to fit in the notebooks used in this department. In the first year the 
initiative work is on the principal groups of plants, which is a little 
difficult for the beginner, and interest has been stimulated by periods 
of debates. A Biological Club has been organized; a program is 
arranged, and the discussions are illustrated with the lantern. In 
the second year the subject matter has been presented in groups 
according to their natural relationships. Two hundred and fifty-four 
types of drugs have been arranged in twelve-ounce jars, which have 
been consulted at recess and other times ; the reviews have been of 
great help also. The third-year work has been in the study of choco- 
late products, spices, and a number of National Formulary drugs. 
Professor Kraemer, having been relieved of the teaching in Bacteri- 
ology, has been enabled to develop a special course in Microscopy 



^./gust;i9u ra '} Philadelphia College of Pharmacy. 385 

for the Special Chemical students. It is suggested that time be 
provided for compulsory botanical excursions to be considered as 
part of the laboratory exercises. The green-house and roof garden 
continue to be very serviceable in giving instruction. 

Department of Analytical Chemistry: The instruction in this 
department has been carried on in accordance with the published 
announcement and outlined course. The results have been very 
satisfactory, and a continuance along the same lines is recommended. 

Department of Bacteriology: The attendance at lectures was uni- 
formly good. The laboratory instruction in the regular course will 
be doubled. 

Department of Physical Culture: About two-thirds of the class 
presented themselves for examination. New record cards have been 
prepared. Many of the students were found to be under weight and 
Hat-chested, and the proper gymnastic training for these conditions 
was given. 

Physical Director: This report contains a number of interesting 
items on the work of the department. 

May 5, 1914. — Eighteen members present. 

Committee on Library reported 472 books shelf -listed, making 
a total of 7690 books ready to be catalogued. Use of Library for 
the month by 382 persons. 

Committee on Supplies were given power to act in procuring 
additional microscopes. 

Committee on Examinations reported having received a com- 
munication from the Secretary of the State Pharmaceutical Exam- 
ining Board, requesting that the final result of the third-year exam- 
inations be recorded in time to comply with the State Board require- 
ments. 

President Howard B. French presented to the College, on behalf 
of Mrs. Mary I. Banks, a check for $5000 with which to establish 
a fellowship in memory of her father, the late Clayton French. 
The following resolution was adopted : 

Resolved, That the Board of Trustees of the Philadel- 
phia College of Pharmacy gratefully acknowledge 
receipt of Five Thousand Dollars through the 
hands of Mr. Howard B. French from Mrs. Mary 
I. Banks, to be used in establishing a fellowship 
in honor of her father, the late Clayton French. 



3 86 



Osage Orange as Commercial Dyestuff. { Am ±*™* t ' SS™' 



Resolved, That a tablet be erected in the hallway of 
the College bearing- the following inscription : 

1824 1890 

Clayton French 

FELLOWSHIP 
Established by his daughter 

Mary I. Banks 

May 16th, 1914 

The Dean moved that the gift be accepted and that the grateful 
thanks of the College be expressed. It was further resolved that 
the income from the fund should be used for advanced research work. 

Mr. Campbell referred to the N. A. R. D. Convention to be held 
in August in this city, and favored representation by the College. 
After discussion, a committee of five, consisting of Messrs. Campbell, 
Osterlund, Remington, Mulford, and Evans, was appointed to con- 
sider the matter and report to the Board. 

The Chairman announced the appointment of the Special Com- 
mittee on Panama Exposition : Joseph P. Remington, chairman ; 
Joseph W. England, Warren H. Poley, H. K. 'Mulford, C. Stanley 
French; associates, Professors E. F. Cook, F. X. Moerk, Henry 
Kraemer. With authority to add to their number. 



OSAGE ORANGE, ITS VALUE AS A COMMERCIAL 
DYESTUFF. 

It has long been known in the Southwest that the wood of the 
Osage orange tree contains a dyestuff that would give a more or 
less fast yellow color. An examination of the wood from Texas by 
F. W. Kressmann showed that it not only contains moric acid and 
morintannic acid, the same as fustic wood, but also that the dyeing 
principles are present in amount to be commercially valuable. A 
comparative series of dyeing experiments made with fustic and 
Osage orange wood and extracts showed the latter to be of equal 
value with fustic in regard to depth of colors produced, the 
amount of extract, the character of the dyeing, and fastness to 
light, weather, washing, etc. — Science, vol. xl, July 3, 1914, p. 37. 



THE AMEEIOAN 



JO 



Rrog^NUS p^j%hiAna: its history, growth, 

METj$$$JS OF CpLI/ECTION AND BIBLIOGRAPHY. 




AL OF PHARMACY 



^QfiPTEMBER, 1 91 4 



Johnson and Edith Hindman. 



Rhamnus Purshiana was discovered in Montana, on the banks 
of a tributary of the Columbia River, in 1805 or 1806, by the mem- 
bers of the first North American transcontinental exploring expe- 
dition under the command of Lewis and Clark (" Silva of North 
America," by Sargent, vol. 2, 1895, pp. 37-40). It was also found 
by Lewis and Clark in what is now known as Oregon and Washington. 
On their return journey they took with them a specimen of the 
shrub for identification. The exact place where Lewis and Clark 
collected the type, later examined by Pursh, was Camp Chopunish, 
situated on the east bank of the Kooskooskee (Clearwater) River, 
about two miles below what is now known as Kamiah, Idaho (Con- 
tributions from the National Herbarium, vol. 11, "Flora of Wash- 
ington," by Piper). 

This plant, along with a number of other unknown botanical 
specimens collected on the journey, was given to Frederick Pursh, 
a German botanist, of Philadelphia, for botanical study. Frederick 
Pursh lived in America between the years 1799 and 1812. In 1812 
he went to London, where, in 1814, he published a description of 
the plant, giving it the name of Rhamnus alnifolia (" Flora America? 
Septentrionalis," vol. 1, 1814, p. 166). 

Augustin Pyramus de Candolle (1 778-1841) found that another 
plant had been named Rhamnus alnifolia by C. L. de Brutelle 
L'Heritier in 1775. In 1825 he changed the name of the plant de- 
scribed and named by Pursh as Rhamnus alnifolia* to Rhamnus 
Purshiana, in honor of Pursh (de Candolle, "Prodromus Systematis 
Naturalis," vol. 2, 1825, p. 25). 

The following is a translation of the Latin description of Rhamnus 



(387) 



3 88 



Rhamnus Purshiana. 



f Am. Jour. Pharm. 
( September, 1914. 



alnifolia by L'Heritier, Rhamnus alnifolia by Pursh, and Rhamnus 
Purshiana by de Candolle, as copied in Latin by John Uri Lloyd from 
the original works in the Lloyd Library, Cincinnati, Ohio • 

Rhamnus alnifolius (L'Heritier, " Sertulum," p. 5), erect; leaves 
oval, serrulate, veins straight, pointed obliquely toward the end, under 
surface smooth, with flowers dioecious ; peduncle one flowered, with 
calyx acute, fruit top shaped. 

Rhamnus alnifolius (Pursh), R. inermis (unarmed or without 
thorns) ; leaves oval, denticulate, short acuminate; base cordate and 
slightly curved, veins underneath covered with hairs; peduncle split 
twice into two parts, berry globose but depressed. On the banks of 
the river Kooskooskee. Berries purple, very highly esteemed by the 
Indians of that country. (Pursh s " Flora American Septentrionalis," 
vol. 1, 1814, p. 166.) 

Rhamnus Purshianus (de Candolle J, erect; leaves oval, denticu- 
late, short acuminate, cordate and slightly curved, veins underneath 
covered with hairs, peduncle split twice into two parts, berry globose 
but depressed. On the banks of the river Kooskooskee. Rhamnus 
alnifolius (Pursh, "Flora," vol. 1, p. 166, not L'Heritier) (" Pro- 
dromits Systematis Naturalis Regni Vegetabilis," by de Candolle, 
vol. 2, 1825, p. 25). 

Johann Friedrich (Iwan Iwanowitsch) Eschscholtz, a Russian 
naturalist, discovered the plant on the shores of San Francisco Bay, 
California, in 1816, and it was described by him in the " Memoirs of 
the Academy of St. Petersburg," vol. 10, .1826. 

Prof. C. S. Sargent (" Notes on North America Trees," vol. 23; 
Garden and Forest, Feb. 18, p. 75; The Pacific Druggist, April 15, 
1891) states that in 1838 Rafinesque describes in the " Silva Tellu- 
riana " his Personon Laurifolium, his description being drawn from 
a plant which he found in Bartram's Botanic Gardens, in Philadel- 
phia. It is a tree, he says, from the Oregon mountains with elliptical, 
acute, sub-entire, shining, glabrous leaves pubescent on the lower 
surface when young, reniform petals, and slight emarginate 
stigma. The plant in Bartram's Gardens was twenty feet high, 
and the berries formed fine clusters and assumed three colors, being 
by turn green, red, and black when fully ripe. This is the earliest 
record of the cultivation of Rhamnus Purshiana, for there does not 
seem to be much doubt that it was this plant that Rafinesque had in 
mind. Certainly there is no other tree from the mountains of 
Oregon which could be made to answer to this description. If Lewis 



Am. Jour. Fharm. ) 
September, 1914. / 



Rhamnus Purshiana. 



389 



and Clark, as is possible in the case of the plant o^ whose medicinal 
value they must have learned from the Indians, had brought home 
seed, these might very well have produced by 1838 trees twenty feet 
in height. 




Fig. i.— A Cascara tree on University of Washington campus. 



Rhamnus Purshiana is claimed to have been known since the 
early part of the nineteenth century to the Mexicans and Spanish 
priests of Old California. Tt was known by the Spanish name of 



39Q 



Rhamnus Purshiana. 



\ Am. Jour. Pharm. 
( September, 1914. 



Cascara Sagrada^ (sacred bark), so named because the wood was 
supposed to be identical with the "Shittim " or " Chittim " wood 
used in the building of the Ark of the Covenant. 

Common Names. — In the different localities where it grew the 
tree was known by the Indians and early white settlers by the follow- 
ing names : Bearberry, Barberry, Coffee-berry, Coffee-tree, Bitter- 
bark, Bear-wood, Wahoo, Shittim-wood, Chittim-wood, and Cas- 
cara Sagrada. 

Range. — Rhamnus Purshiana is widely distributed throughout 
the Northwest. It is found in small quantities at the head of the 
Portland canal and mouth of the Cnuk River in Southeastern Alaska 
and in northern British Columbia, in commercial quantities on the 
west slope of the Cascade Mountains of southern British Columbia, 
Washington, Oregon, and northern California. 

It grows in the Mission Mountains and near the Flat-head Lake 
in Montana, in the Bitter-root Mountains and Seven-Devil Moun- 
tains in Idaho. It occurs occasionally on the eastern slope of the 
Sierra Nevada Mountains, and then reappears in the mountains of 
Colorado and western Texas. In one of its forms it is scattered 
throughout the mountainous regions of southern California, Arizona, 
New Mexico, and northern Mexico. 

Commercial Range. — The tree grows abundantly and attains 
its greatest size on the western slope of the Cascade range of moun- 
tains in Washington, Oregon, northern California, and southern 
British Columbia. Plenty of moisture and a slightly sandy soil are 
favorable factors for its rapid development. 

It is usually found in small river bottoms, sides and bottoms of 
canyons, growing under the shelter of coniferous forests, around the 
edges of swamps, and on slightly elevated moist areas. 

With favorable soil and moisture the tree frequently springs up 
in places formerly covered with coniferous trees that have been 
destroyed by fire. It is seldom found in broad river bottoms or 
valleys on account of being crowded out by the more thrifty and rapid- 
growing alder and cottonwood trees. 

The tree is found at sea level and up to an altitude of 1800 to 
2000 feet. Men working in the cascara forests of Washington state 
that the tree grows to a height of twenty to thirty feet and attains 
an average diameter of six to eight inches. Trees having a diameter 
of three feet have been found. Sargent (" Silva of North America," 
vol. 2, p. 37) states that the tree attains a height of thirty-five to 



Am. Jour. Pharm. > 
September, 1914. / 



Rhamnus Purshiana. 



391 



forty feet with a diameter of eighteen to twenty inches. In shady 
places the tree grows tall, straight, and slender, while in open places 
with plenty of sunlight it branches near the base, attains greater 
diameter and less height. 

A mild, moist climate is necessary for the abundant growth and 
large size of the tree. In a dry climate and higher altitude it occurs 
sparingly and in shrub form only. In its most northern range, in 
Southeastern Alaska, it also grows as a shrub of three to six feet in 
height. In certain sections of the California coast it has a height 
of only a few inches with prostrate stems. 

Reforesting. — Opinion differs as to the natural reforesting of 
cut-over areas. It is stated by some that a new growth always 
springs up on cut-over areas, providing the bark is not removed from 
the stumps; while others claim that sprouts rarely spring up from 
stumps, because the trees are usually cut while the sap is running, 
hence very little life is left in the stump. 

The tree is a prolific seeder ; seeds are of medium high germination 
(often tardy) and of very persistent vitality. Scattered seedlings 
are fairly abundant in moist forests, litter and mucky soils ; scanty 
in drier habitat, except in depressions where seeds have been deeply 
covered by accident. (Geo. B. Sudworth, U. S. Department of 
Agriculture, Forest Service Bulletin, " Forest Trees of Pacific Slope," 
1908, p. 404.) 

Longevity. — The longevity has not been fully determined for 
large trees. Trees ten years old are from six to eight inches in 
diameter. Trees estimated at twenty-five to forty years old are fre- 
quently found. 

Cultivation. — For several years the U. S. Department of Agri- 
culture has conducted experiments looking towards the cultivation 
of this tree, and has succeeded in growing it from the seed in moist 
places near Washington, D. C, the trees in six years from the seed 
attaining a height of ten to twelve feet. 

The Kew Gardens in England ten years ago raised cascara sagrada 
from the seed collected in California, and it has proved quite hardy. 
The tree has also been grown in Germany, but is said to develop but 
slowly. 

In the experiments conducted by the Department of Agriculture a 
certain method of pruning has been followed which forces the top of 
the tree into three or four branches; one of these branches may be 
cut each year for peeling, and, as another branch soon develops in its 



392 Rhamnus Purshiana. {^S^dS^mA 

place, this will be ready for cutting in a few years, the other branches 
in the meantime having been treated in the same way. 

Seed of Rhamnus Purshiana is not on the market, but would 
have to be collected by some one in the cascara region. (Alice Henkel, 
" The Cultivation of Medicinal Plants," The Druggists' Circular, 
March, 1912, p. 133.) 

The following is a description of the bark, leaves, flowers, and nut- 
lets of Rhamnus Purshiana by Sargent (" Silva of North America," 
vol. 2, pp. 37-40). 

The bark of the trunk, even on old trees, is rarely more than a 
quarter of an inch thick, and varies in color from dark brown to 
light brown or gray tinged with red, the surface being broken into 
short, thin scales. The branchlets, when they first appear, are 
coated with fine, soft pubescence; they are pale yellow, green, or 
reddish-brown, and are pubescent, glabrous, or covered with scat- 
tered hairs in their second season, when they are marked with large, 
elevated scars left by the falling of the leaves. 

The leaves are alternate, elliptical-oblong, obovate, acuminate, or 
broadly elliptical, and are obtuse, acute, or bluntly pointed at the 
apex, rounded sub-cordate, or sometimes wedge shaped at the base, 
and serrulate, denticulate, obscurely crenate, or often merely entire 
with wavy margins. They are thin membranaceous or sometimes 
thick and coriaceous, and are glabrous or pubescent with scattered 
hair on the lower surface and along the veins on the upper surface. 
They vary from an inch to over seven inches in length, and are con- 
spicuously netted veined, with broad and prominent mid-ribs and 
primary veins ; they are borne on stout, often pubescent, petioles 
one-half inch or an inch long, and are sometimes pale yellow-green 
above and below, and sometimes dark green and rather opaque 
above and paler and often somewhat orange color or brown on the 
lower surface. 

In Washington and Oregon and at high elevations in the moun- 
tains the leaves fall late in November, having previously turned 
pale yellow. Farther south and near the California coast they re- 
main on the branches almost all winter, or until the following 
spring. The stipules are membranaceous, acuminate, and nearly 
deciduous. 

The flowers are produced on the young shoots in axillary um- 
bellate cymes or slender, pubescent peduncles varying from one- 
half to nearly an inch in length. The pedicels are slender, pubescent, 



Am. Jour. Pharm. ) 
September, 1914. J 



Rhamnus Purshiana. 



393 



a quarter of an inch to almost an inch long and four to five times 
longer than the calyx, which is narrowly campanulate with more 
or less spreading acuminate lobes. The petals are minute, ovate, 




Fig. 2. — Peeling Cascara bark in Washington forests. Illustrating a method employed in 
commercial collection, and the dense forest in which the collector must work. 

and deeply emarginate at the apex, and enfold the short stamens, 
whose filaments are somewhat thickened at the base. The style 
is crowned with a slender two-lobed stigma. The fruit globose or 
broadly obovoid, a third to one-half inch in diameter and very 



394 



Rhamnus Purshiana. 



Am. Jour. Pharm. 
September, 1914. 



slightly or not at all lobed, with thin, rather juicy pulp and two or 
three nutlets. It is at first green, then red, and finally black at 
maturity. 




Fig. 3. — Cutting Cascara tree in Washington forests. 

The nutlets are obovate, usually a third to an inch long, rounded 
on the back, and flattened on the inner surface by mutual pressure, 
with two bony, tooth-like enlargements at the base, one on each 
side of the large scar of the hilum, and a thin gray or pale yellow- 



Am. Jour. Pharm. ) 
September, 1914. J 



Rhamnus Purshiana. 



395 



green shell. The testa of the seed is thin and papery, its outer 
surface of a yellow-brown color and its inner surface like the 
cotyledons, bright orange color. 

Characteristics of the Wood. — The wood of Rhamnus Pur- 
shiana while green is soft and brittle, but when dry it is tough and 
hard. After the bark is removed from the wood it checks very 
easily on drying. It is used to some extent in making ax-handles 
and wagon spokes. 

Collection of Bark. — The season for peeling and collection of 
the bark is during the months of April to September. The tree is 
usually cut down and the bark removed from every part except 
the smallest branches. Trees of four inches or less in diameter 
are not cut, because the bark is too thin. Foreign material, such as 
sand, moss, etc., is removed by scraping; the common curry comb 
is the convenient tool. Those who peel on a small scale usually 
prepare very clean bark, while those who work on a larger scale are 
frequently careless in removing foreign matter. Much of the bark 
is collected by small ranchers and Indians living in the vicinity of the 
cascara areas. Larger quantities are collected by companies, who 
• employ a number of men for this purpose during the season of 
collection. 

Curing of the Bark. — After being mossed the bark is spread out 
on the ground on tarpaulins or on racks in the sunshine to cure. 
Sometimes it is kept under cover during the curing period. If placed 
in direct sunlight it usually takes about four days for the curing 
process. About 60 per cent, of its weight is lost during the curing 
stage. If not rained upon the bark will cure with a rich satin brown 
color, while if rained upon it will be spotted with black or become 
entirely black. Slow, careful drying yields bark 10 per cent, heavier 
than if hastily dried. The bark when dry is broken into small pieces, 
usually by means of a feed chopper, then packed into sacks holding 
from 50 to 100 pounds and stored in a dry place. The collector of 
the bark seldom keeps it during the aging period of one to two 
years. The season's collection is, as a rule, contracted for before 
peeling begins, and the product is shipped early in the fall. The 
dried bark must be carefully kept, otherwise it will absorb moisture 
and deteriorate. 

Prices and Production. — When first introduced to commerce 
the bark of cascara sagrada commanded a price of fifty to sixty cents 
per pound. The supply, however, rapidly increased and prices fell 



396 



Rhamnus Purshiana. 



( Am. Jour. Pharm. 

\ September, 1914. 



during the next few years. The following table presents data on 
prices and annual production of the bark for the last decade, as 
compiled from the files of the Oil, Paint and Drug Reporter by 
Rodney H. True (The Pharmaceutical Era, January, 1913, p. 9) : 



Year. 


Highest price 


Lowest price 


Estimated quantity 


per pound. 


per pound. 


of bark peeled. 




5-5 


cents 


4-5 


cents 


500-600 tons. 


1902 


6.0 


cents 


4.75 cents 


450 tons. 


1903. • • • 


22.5 


cents 


10.0 


cents 


1000 tons. 


1904 


17.00 cents 


7.0 


cents 


750-1500 tons. 


1905 


7-0 


cents 


5.5 


cents 


850 tons. 


IOX)6 


11.0 


cents 


5.5 


cents 


200 tons. 


I907 


10.5 


cents 


8.5 


cents 


250-600 tons. 


1908 


9-5 


cents 


6.5 


cents 




I909 


8.5 


cents 


7.0 


cents 




I9IO 


7-5 


cents 


7.0 


cents 


550-^600 tons. 


I9II 


90 


cents 


7.5 


cents 


1000-2000 tons. 


1912 


10.5 


cents 


8.0 


cents 


500 tons. 



Stewart & Holmes Drug Company, of Seattle, Wash., states 
that the average price of the bark on the Pacific coast for 1913 was 
5 cents per pound, and the yield was estimated at 1200 to 1500 tons. 
It is estimated that 'about 50 per cent, of the annual yield is ex- 
ported to Europe, the remainder being shipped to eastern drug 
manufacturers of the United States. 

Future Supply. — Cascara dealers have been predicting for 
more than a quarter of a century that the supply would soon be 
exhausted, but each year the yield is sufficient to meet the demand. 
The greater portion of the easily accessible trees have been cut, 
therefore the collectors must find new fields, which are naturally 
more remote from transportation. 

Collectors usually leave standing trees under four inches in 
diameter, because of the thin bark, which insures reproduction on 
cut-over areas. The vast holdings of large timber companies con- 
tain thousands of tons of cascara, but they will not permit the 
peeling of these trees. This fact, together with the fact that new 
trees are growing on tracts that have been peeled once or twice 
before, insures a supply of bark for many years. 

Description of the Cured Bark. — It is usually in flattened or 
transversely curved pieces, occasionally in quills two to ten centi- 
metres long, and three centimetres in diameter, bark one to three 
millimetres thick; outer surface dark brown or brownish red, fre- 
quently completely covered with grayish or whitish lichens, several of 



Am. Jour. Pharm. ) 
September, 1914. j 



Rhamnus Purshiana. 



397 



which are peculiar to this bark, and with small groups of brownish 
apothecia, longitudinally striate, turning red when moistened with 
solutions of the alkalies; fracture short, with projections of bast 
fibres in the inner bark, the medullary rays one or two cells wide, 
forming converging groups ; in cross section this inner surface of 
the bark indistinctly crenate ; odor distinct ; taste bitter, slightly acrid. 
(Dr. Henry Kraemer, " Botany and Pharmacognosy," 3rd Edition, 
P- 524.) 




Fig. 4. — Packing Cascara bark to trail. Because of the underbrush and fallen timber horses 
cannot be used except on trails. 



Description of the Powdered Bark. — The powdered bark is 
light brown ; bast fibres long, much thickened, lignified ; stone cells 
very thick-walled, about 50 fi in diameter, crystal fibres containing 
monoclinic Crystals of calcium oxalate; calcium oxalate also, in 
rosette aggregates or monoclinic prisms 5 to 20 fx in diameter ; starch 
grains spherical, about 4 ^ in diameter; parenchymatous cells with 
yellowish contents colored red with alkalies. (Dr. Henry Kraemer, 
" Botany and Pharmacognosy," 3rd Edition, p. 759.) 

Structure of the Bark.— The bark as described by Prescott 
consists of three parts ; namely, the corky layer, the middle bark, and 
the inner bark. 



398 



Rhamnus Purshiana. 



f Am. Jour. Pharm. 
( September, 1914. 



The corky layer consists of an outer epidermis of dark brown 
weathered cells, then several rows of cells filled with a dark red 
coloring matter, and in the more recent bark a row or two of cells 
containing chlorophyll. 

The middle bark is made up of parenchymatous cells, which are 
filled with small starch grains. There are visible, also, in the trans- 
verse section, several groups of cubical crystals and in the longitudinal 
section groups of very thick-walled yellow cells. 

The inner bark consists principally of yellow medullary rays, 




Fig. 5- — Transporting Cascara bark on pack horses to wagon road. 



separated by bast parenchyma, through which are scattered numerous 
yellow bast fibres. As seen in the longitudinal section, these fibres 
are frequently surrounded by small cubical crystals. (Parke, Davis 
and Company, " New Preparations," Feb. 5, 1879; " Proc. of Amer. 
Pharm. Assoc.," vol. 27, 1879, p. 262.) 

Microscopical Examination of the Bark. — The corky layer 
is about 0.045 mm - thick, and consists of eight or twelve -rows, some- 
what flattened, rather thick-walled, but not sclerotic cells. The 
parenchyma of the primary bark is tangentially elongated, partly of a 
collenchymatic character, free from secondary cork, and contains 



Am. Jour. Pharm. ) 
September, 1914. j 



Rhamnus Purshiana. 



399 



scattered groups of roundish stone cells, with very thick walls, and 
accompanied by single rhombohedric crystals ; the thin-walled paren- 
chyma contains numerous groups of crystals. The inner bark con- 
sists of medullary rays composed of two or three rows of thin-walled, 
somewhat radially elongated cells, and of broader bast rays in which 
the parenchyma cells are coarsely dotted upon the radial and horizon- 
tal walls, and loosely united in a tangential direction ; the sieve-tubes 
are larger, irregularly angular, and united, to the number of four or 
six, by means of coarsely porous sieve-plates, and on the radial sides 
marked with roundish sieve fields; the bast fibres form alternate 
groups of two or three rows, extending into few bast rays, and are 
surrounded by crystal cells. (Dr. J. Moeller, Pharm. Centralhalle, 
No. 28, 1882; 11 Proc. A. Ph. A.," vol. 31, 1883, p. 166.) 

History of Rhamnus Purshiana in the Medical Profession. 
— J. Winchell Forbes {Practical Druggist, Aug., 19 10, p. 48) states 
that cascara bark was brought to the notice of the public in 1872 by a 
man named Donnelly, who learned of its virtues from the Catholic 
priests and Indians of Oregon and northern California. The priests 
called the tree " shittim wood," claiming that it was identical with 
that used in making the Holy Ark, and for this reason the bark was 
called cascara sagrada (sacred bark) . 

Under the direction of Mr. Forbes, Donnelly made a preparation 
of the bark by macerating it in cider vinegar for two weeks. This 
preparation was sold as a patent medicine under the name of 
" Donnelly's Discovery," which appears to have been the earliest 
commercial use of the bark. 

In a paper contributed to " New Preparations " (Parke, Davis 
and Company, Oct. 15, 1877, p. 8), Dr. J. H. Bundy, an eclectic 
physician of Colusa, Cal., commended cascara sagrada as a valuable 
remedy in the treatment of constipation. In January, 1878, Dr. 
Bundy contributed a paper on the subject of cascara sagrada in which 
he gave the uses of its fluidextract. 

To Dr. J. H. Bundy, 1877, is due the credit of introducing the 
bark of Rhamnus Purshiana (cascara sagrada) to the medical pro- 
fession. In 1877 he shipped a quantity of the bark to Parke, Davis 
and Company, of Detroit, Mich., who in 1878 made the first phar- 
maceutical preparation (the fluidextract). To Parke, Davis and 
Company is therefore due the credit of bringing a preparation of this 
drug to the attention of physicians and pharmacists. Parke, Davis 
and Company were for a number of years the sole manufacturers of 



40o 



Rhamnus Purshiana. 



I Am. Jour. Pharin. 
\ September, 1914. 



preparations of this drug. (" Proc. of the Amer. Pharm. Assoc.," 
vol. 44, 1896, p. 198 ; Practical Druggist, August, 1910, p. 48 ; Bulletin 
of the Lloyd Library, No. 18, 191 1, pp. 68, 69.) 

Parke, Davis and Company state in one of their publications that 
they brought cascara sagrada to the notice of the British Medical 
Association at Cork in 1879. 

Dr. C. H. Adair, of Colusa, Cal., a partner of Dr. Bundy, sent, 
in 1878, specimens of the bark and botanical specimens of the tree 
yielding it to J. U. Lloyd, of Cincinnati, Ohio. These, on identifica- 
tion by Curtis G. Lloyd, proved to be Rhamnus Purshiana, thus 
establishing the drug's botanical position. (" Proc. of the Amer. 
Pharm. Assoc.," vol. 44, 1896, p. 198; Bulletin of the Lloyd Library, 
No. 18, 191 1, p. 70.) 

In 1880 George W. Kennedy first published a formula for an elixir 
of Rhamnus Purshiana. (" Proc. of the Amer. Pharm. Assoc.," 
vol. 28, 1880, p. 431.) 

Prof. W. T. Wenzell, in 1883, published a formula for an elixir of 
cascara sagrada, using potassium carbonate to remove the bitter prin- 
ciple. (" Proc. of the Cal. Pharm. Soc," 1883; Amer. Jour, of 
Pharm., May, 1883, p. 252; " Proc. of the Amer. Pharm. Assoc.," 
vol. 31, 1883, p. 82.) 

Mr. James G. Munson, a druggist of San Jose, Cal., in a letter 
to the writers under date of January 24, 1914, claims to have been 
the first to discover how to make tasteless fluidextract of cascara 
sagrada by the magnesium oxide process. This was in the fall of 
1886, while he was in the employ of Prof. W. M. Searby, of San 
Francisco, Cal. Mr. Munson, however, did not publish a formula 
for the preparation, and the method remained a trade secret. (The 
Pacific Druggist, June 15, 1890, p. 27.) 

Dr. Fred A. Grazer, of Sacramento County Hospital, Sacramento, 
Cal., in a letter to the writers under date of November 21, 1913, 
states that Prof. W. M. Searby, of San Francisco, Cal., was the first 
to introduce a preparation of bitterless fluidextract of cascara sagrada 
which was offered for sale by retail druggists. The method of manu- 
facture was a secret process, no formula being published. Dr. Grazer 
published the first formula for the preparation of a bitterless fluid- 
extract of cascara sagrada, using calcined magnesia to remove the 
bitter principle. (P har mac cutis che Rundschau, Jan., 1888, p. 9; 
" Proc. of the Amer. Pharm. Assoc.," vol. 36, 1888, p. 253.) 

Parke, Davis and Company, of Detroit, Mich., in their pamphlet 



Am. Jour. Pharm. 1 
September, 1914. J 



Rhamnus Purshiana. 



401 



on " Cascara Sagrada and its Preparation," state that they have a 
formula (No. 536), under date of 1887, for the manufacture of 
aromatic (tasteless) fluid cascara sagrada. 

R. Wright published, in 1888, a formula for a bitterless fluid- 
extract of cascara sagrada, .using calcined magnesia to remove the 
bitter principle. (" Yearbook of Pharmacy," 1888, pp. 395, 396; 
" Proc. of the Amer. Pharm. Assoc.," vol. 37, 1889, p. 381.) 

Prof essor John M. Maisch (" Proc. of the Amer. Pharm. Assoc.," 
vol. 38, 1890, p. 394) calls attention to the fact that H. R. Slack, Jr., 




Fig. 6. — Sun-drying Cascara bark on platform of abandoned saw-mill. 



recently recommended Rhamnus Purshiana for pharmacopceial recog- 
nition before the Georgia Pharmaceutical Association. 

The bark first became official in the United States Pharmacopoeia 
in the 1890 edition. 

History of the Chemistry of Rhamnus Purshiana. — The 
first chemical examination of the bark was made by Dr. A. B. 
Prescott, who isolated a brown resin of strong, bitter taste, colored 
vivid purple- red by potassium hydroxide solution ; a red resin, nearly 
tasteless, colored rich brown by potassium hydroxide solution ; a 
yellow resin or a neutral body, tasteless, colored bright red-brown by 
sulphuric acid, not colored by potassium hydroxide solution. He also 



402 



Rhamnus Purshiana. 



( Am. Jour. Pharm. 
( September, 1914.. 



isolated a crystallizable body in white double pyramids, and some 
other form of dimetric system. Tannic acid, oxalic acid, malic acid, 
a fixed oil, a volatile oil, wax, and starch were also found. (Amer. 
Jour, of Pharm., vol. 51, 1879, P- I ^ > 5-) 

Limousin (Jour, de Pharm. et de Chim. (5), vol. 6, 1885, p. 80; 
" Proc. of the Amer. Pharm. Assoc.," vol. 33, 1885, p. 188) con- 
sidered that the resins obtained by Prescott were derived from 
chrysophanic acid, which he believed to be present in notable quan- 
tities. According to H. A. D. Jowett (" Proc. of the Amer. Pharm. 
Assoc.," vol. 52, 1904, p. 288) these deductions are incorrect. He 
believes that emodin, which he claims is present, will give the char- 
acteristic reactions thought to be due to chrysophanic acid. 




Fig. 7- — A means of moving dried Cascara bark to bark cutter. 



W. T. Wenzell (Pharm-. Runds., vol. 4, 1886, p. 79) isolated from 
the bark a small quantity of an orange-red, crystalline substance, 
melting at 226°-230° C, and having the properties of a glucoside. 
Later investigators have shown that it was impure emodin. 

H. F. Meier and J. L. Webber (Amer. Jour, of Pharm., vol. 60, 
1888, p. 87) found, as a result of their investigation, a glucoside, a 
ferment, glucose, and traces of ammonia. 

Paul Schwabe (Archiv, der Pharm., vol. 226, 1888, p. 569) ex- 
amined Rhamnus Purshiana and found emodin, identical with that of 
Rhamnus frangula, to exist as such in the bark, and identified it by 
means of its acetyl and di-bromo compounds, all of which were 



Am. Jour. Pharm. ) 
September, 1914. / 



Rhamnus Purshiana. 



403 



analyzed. He considered that Wenzell's crystals, previously referred 
to, were merely impure emodin, and could obtain no evidence of the 
existence of a glucoside, nor could he isolate any other crystalline 
substance. 

Dr. Eccles reports in the Druggists Circular of March, 1888, 
p. 54, the discovery of the presence of an alkaloid which he states he 
has separated from the fluidextract and precipitated by Mayer's 
reagent. 

A. C. Zeig (" Proc. of the Amer. Pharm. Assoc.," vol. 37, 1889, 
p. 261 ) further examined the resins previously described by Prescott, 
but was unable to isolate any definite principle. 

Le Prince (Compt. rend., vol. 115, 1892, p. 286) claims to have 
obtained the active principle of cascara bark in a crystalline form and 
named it cascarine. Le Prince suggested that cascarine might be 
identical with rhamnetin. 

A most curious confusion has arisen in chemical literature with 
respect to this substance. Beilstein (" Handbuch," 3rd edition, vol. 3, 
p. 627), under cascarine, states that it is identical with rhamnetin, 
but Phipson (Compt. rend., vol. 115, 1892, 474) considers that it was 
identical with xantho-rhamnin, and Van Rijn (" Die Glykoside," 
1900 edition, p. 299), without comment, accepts this latter statement, 
and under xantho-rhamnin gives the details of Le Prince's prepara- 
tion of cascarine from cascara, 

The properties of cascarine, as given by Le Prince, prove that it 
could not be identical with either rhamnetin or xantho-rhamnin. 
Le Prince presents no evidence of the purity of cascarine ; it agrees, 
however, in properties, with the exception of the melting-point, with 
emodin. 

E. Cabanes states that the active principles of cascara bark are 
located in the layers of bast immediately adjoining the cambium, and 
in the medullary rays traversing these layers. {Pharm. Jour., May 2, 
1896, p. 343 ; Rep. de Pharm. (3), vol. 7, p. 97 ; " Proc. of the Amer. 
Pharm. Assoc.," vol. 44, 1896, p. 638.) 

A. R. L. Dohme and H. Englehardt (" Proc. of the Amer. Pharm. 
Assoc.," vol. 45, 1897, p. 193) examined Rhamnus Purshiana and 
claimed to have isolated the active principle of the drug, which they 
named Purshianin. This was stated to be a glucoside, yielding, on 
hydrolysis, emodin and a sugar which was not identified. They con- 
sider the fat to be a mixture of dodecyl palmitate and stearate. They 
also attempted to obtain the bitter principle in a crystalline form, but 
were unsuccessful. 



404 



Rhamnus Purshiana. 



l Am. Jour. Pharm. 
\ September, 1914. 



H. A. D. Jowett (" Proc. of the Amer. Pharm. Assoc.," vol. 52, 
1904, p. 295) summarizes the results of previous investigators as 
follows : 

I. The only definite principle isolated from cascara bark, the 
identity of which can be considered to be absolutely established, is 
emodin. 

2. The statement of the existence in the bark of chrysophanic acid, 
chrysarobin, or glucosides yielding on hydrolysis emodin, chryso- 
phanic acid, or rhamnetin, is not supported by satisfactory experi- 
mental evidence. 




Fig. 8. — Cutting and sacking dried Cascara bark. 



3. Wenzell's " crystals," Le Prince's " Cascarine," and Dohme 
and Engelhardt's " Purshianin " would appear, from the descriptions 
given by the respective authors, to be merely impure emodin. 

4. No indication can be given of the identity of the crystals 
described by Prescott. 

5. It has been stated by Dohme and Engelhardt that the fat of 
cascara consists of dodecyl palmitate and stearate. 

Mr. Jowett (" Proc. Amer. Pharm. Assoc.," vol. 52, 1904, 
pp. 288-295), in his investigations, confirmed the presence of emodin 
in cascara, and also isolated a substance which he called isoemodin. 
He also found glucose and syringic acid. No evidence was obtained 
of the existence of chrysophanic acid, chrysarobin, or glucosides 
yielding on hydrolysis emodin, chrysophanic acid, or rhamnetin. 



Am. Jour. Tharm. ) 
September, 1914. J 



Rhamnus Purshiana. 



405 



No substance corresponding to either cascarine or purshianin was 
found. The fat was found to consist of rhamnol arachidate and free 
arachidic acid. A hydrolytic enzyme was isolated. The bitter and 
the active principles of the bark were not isolated. 

Chemical Constituents. — The chemical constituents of 
Rhamnus Purshiana are being studied by the writers, and the results 
of the investigation will appear in a later issue of this journal. 

Acknowledgments. — The authors wish to express appreciation 
to Dr. John Uri Lloyd, of the Lloyd Library, Cincinnati, Ohio, and 
Dr. John M. Francis, of Parke, Davis and Company, Detroit, 
Mich., for historical facts ; to Prof. Hugo Winkenwerder, dean of 
the University of Washington College of Forestry, for facts con- 
cerning Rhamnus Purshiana in the State of Washington ; to Dr. Fred 
A. Grazer, of Sacramento, Cal., and Mr. James G. Munson, of 
San Jose, Cal., for facts relating to the first bitterless preparations 
of the bark ; to Mr. Floyd E. Ryus, of Ketchikan, Alaska, for in- 
formation concerning the growth of the tree in Alaska ; to Mr. Carl L. 
Kurtz, of Notus, Idaho, for information concerning its growth and 
range in Idaho; to Mr. H. E. Holmes, of Stewart & Holmes Drug 
Company, Seattle, Wash. ; Mr. Geo. D. Prigmore, a druggist, of Che- 
halis, Wash., and Mr. Charles A. Richey, of Seattle, Wash. , for data 
concerning the growth of the tree and collection of the bark in 
Washington. 

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Am. Jour. Pharm. ") 

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1888. Cascara Sagrada, Formula for Bitterless Fluidextract, by R. Wright. 



408 



Rhamnus Purshiana. 



f Am. Jour. Pharm. 

t September, 1914. 



Yearbook of Pharmacy, 1888, pp. 395-6; Proc. Amer. Pharm. 

Assoc., vol. 37, 1889, p. 381. 
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vol. 38, 1890, p. 494. 
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P. 837. 

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Proc. Amer. Pharm. Assoc., vol. 39, 1891, p. 452. 



Am. Jour. Pharm. 1 
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409 



1891. Rhamnus Purshiana, by H. H. Rusby. The Pacific Druggist, May 15, 
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Compt. rend., vol. 115, Oct., 1892, p. 286; Pharm. Jour, and Trans., 

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1892. Cascara Sagrada, Cascarin, by Phipson. Compt. rend., vol. 115, 1892, 
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1892. Cascara Sagrada, Fluidextract of, by J. W. Turner. Proc. Georgia 

Pharm. Assoc., May, 1892; Proc. Amer. Pharm. Assoc., vol. 41, 

1893, P- 477- 

1893. Cascara Sagrada, Elixir of, by Dujardin-Beaumetz (Gaz. Gynecol.). 

Amer. Jour. Pharm., vol. 65, 1893, p. 75 ; Proc. Amer. Pharm. 
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1894. Cascara Sagrada, Bitterless Fluidextract of, by F. Edel. Amer. 

Drugg. and Pharm. Rec, 1894, p. 259; Proc. Amer. Pharm. Assoc., 
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1895. Cascara Sagrada, Test for Extract of, by E. Bourguelot. Jour, de 

Pharm. et de Chim,, vol. 15, p. 361 ; Proc. Amer. Pharm. Assoc., 
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1895. Cascara Sagrada, Quantitative Determination of Active Principle 

(Emodin), by Victor Schmelik. Nordisk Tidskr., Marz, 1895; 
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1896. Cascara Sagrada, History and Names of, by John Uri Lloyd. Amer. 

Jour. Pharm., vol. 68, Sept., 1896, p. 467; Pharm. Review, Oct., 
1896, p. 225; Proc. Amer. Pharm. Assoc., vol. 44, 1896, p. 198; Bul- 
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1896. Cascara Sagrada, Bitterless, by H. B. Gilpin. Amer. Jour. Pharm., 
vol. 68, March, 1896, p. 135; Proc. Amer. Pharm. Assoc., vol. 44, 
1896, p. 421. 



4 io Rhamnus Purshiana. {^Xrfiiw 

1896. Cascara Sagrada, Bark, Localization of Active Principle of, by E. 

Cabanes. Rep. de Pharm. (3), vol. 7, 1896, p. 97; Pharm. Jour., 

May 2, 1896, p. 343; Pharm. Review, May, 1896, p. 113; Proc. Amer. 

Pharm. Assoc., vol. 44, 1896, p. 638. 
1896. Cascara Sagrada, Bitterless Fluidextract of, by F. Edel. Western 

Druggist, Sept., 1896, p. 391 ; Proc. Amer. Pharm. Assoc., vol. 45, 

1897, P- 423. 

1896. Cascara Sagrada, Aromatic Fluidextract of, Use of Lime, first sug- 

gested by Leo C. Urban. Pharm. Review, Dec, 1896, p. 270; Proc. 
Amer. Pharm. Assoc., vol 45, 1897, p. 424. 

1897. Rhamnus Purshiana, Structure of the Bark, by L. E. Sayre. Amer. 

Jour. Pharm., vol. 69, March, 1897, PP- i 2 6-i34; Proc. Amer. Pharm. 
Assoc., vol. 45, 1897, pp. 564-565 ; Jahresbericht der Pharm., vol. 32, 
1897, p. 179. 

1897. Cascara Sagrada, Review of Previous Experiments, by L. F. Stevens. 

Proc. N. Y. State Pharm. Assoc., 1897, pp. 246-49; Proc. Amer. 
Pharm. Assoc., vol. 46, 1898, p. 869. 

1897. Cascara Sagrada, The Chemistry of, by A. R. L. Dohme and H. 

Engelhardt. Proc. Amer. Pharm. Assoc., vol. 45, 1897, P- J 93- 

1898. Rhamnus Purshiana, Impurity of the Bark, by Holmes. Pharm. 

Jour., 1898, p. 262; Jahresbericht der Pharm., vol. 33, 1898, p. 184; 
Chem. and Drugg., 1898. 

1898. Cascara Sagrada, Bitter Principle of, by A. R. L. Dohme and H. 

Engelhardt. Amer. Jour. Pharm., vol. 70, Sept., 1898, p. 480; Proc. 
Amer. Pharm. Assoc., vol. 46, 1898, p. 340; Amer. Drugg. and 
Pharm. Rec, Sept. 5,, 1898; Jahresbericht der Pharm., vol. 33, 1898, 
p. 184. 

1899. Cascara Sagrada, Aromatic Fluidextract of, by E. H. La Pierre. Proc. 

Mass. State Pharm. Assoc., 1899, p. 54 ; Proc. Amer. Pharm. Assoc., 
vol. 48, 1900, p. 473. 

1900. Cascara Sagrada, Acetic Fluidextract of, by Dr. E. R. Squibb. Amer. 

Jour. Pharm., July, 1900, pp. 311-19; Proc. Amer. Pharm. Assoc., 
vol. 49, 1901, p. 570. 
1900. Cascara Sagrada, Tasteless Fluidextract of, by A. Aweng. Oester. 

Zeitschr. f. Pharm., 1900, pp. 55, 56 ; Proc. Amer. Pharm. Assoc., 
vol. 49, 1901, p. 572. 

1900. Rhamnus Purshiana, Xantho-rhamnin, by Van Rijn. Die Glykoside, 
1900 ed., p. 299. 

1900. Cascara Sagrada, Liquide Alexandre. Proc. Amer. Pharm. Assoc., 

vol. 48, 1900, p. 547. 

1901. Cascara Sagrada, Adulteration of, by Emil Perrot. Jour. Pharm. 

Chim. (6), vol. 15, 1901, p. 161; Pharm. Jour., March 2, 1901, p. 
261 ; Proc. Amer. Pharm. Assoc., vol. 49, 1901, p. 741 ; Brit, and 
Col. Drug., 1901, p. 339; Jahresbericht der Pharm., vol. 36, 1901, p. 
115; Amer. Jour. Pharm., vol. 73, June, 1901, p. 301. 

1902. Cascara Sagrada, Compound Extract of, by H. C. Bradford. Western 

Druggist, Feb., 1902, p. 59; Proc. Amer. Pharm. Assoc., vol. 50, 
1902, p. 712. 



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411 



1902. Cascara Sagrada, Bitterless Fluidextract of, Proposed for National 
Formulary, by C. S. N. Hallberg. Proc. Amer. Pharm. Assoc., 
vol. 50, 1902, p. 489. 

1902. Cascara Sagrada, Tasteless Preparation of, by E. White and R. A. 

Robinson. Amer. Jour. Pharm., vol. 74, Nov., 1902, p. 571 ; Trans. 
Brit. Pharm. Conf., 1902, pp. 420-22; Proc. Amer. Pharm. Assoc., 
vol. 51, 1903, p. 801. 

1903. Rhamnus Purshiana, Description of Tree, by Thomas Howell. Flora 

of Northwest America, vol. 1, Aug. 10, 1903. 
1903. Cascara Sagrada, Valuation of Water Soluble Content, by E. Dow- 
zard. Chem. and Drug., Dec. 12, 1903, p. 990; Proc. Amer. Pharm. 
Assoc., vol. 52, 1904, p. 734. 

1903. Cascara Sagrada, Liquidextract, B. P., by T. P. Gilmour. Pharm. 

Jour., Jan. 24, 1903, p.- 94; Proc. Amer. Pharm. Assoc., vol. 51, 
1903, p. 626. 

1904. Cascara Sagrada, Chemical Examination of Bark, by H. A. D. Jowett. 

Proc. Amer. Pharm. Assoc., vol. 52, 1904, pp. 288-95 ; American 
Druggist and Pharm. Rec, 1904, p. 188; Jahresbericht der Pharm., 
vol. 39, 1904, p. 117. 

1905. Cascara Sagrada, Aromatic Fluidextract of, Adopted in the Com- 

pendium of Canadian National Formulary. Pharmaceutical Era, 
April 27, 1905, p. 471 ; Proc. Amer. Pharm. Assoc., vol. 53, 1905, 
p. 564. 

1905. Cascara Sagrada, Bitterless Extract, Loss of Active Matter, by Pan- 

chaud. Schweisa. JVschr. f. Chem. u. Pharm., vol. 43, 1905, p. 518; 

Proc. Amer. Pharm. Assoc., vol. 54, 1906, p. 628. 
1905. Cascara Sagrada, Habitat, Collection, Supply, etc., by A. E. Zeig. 

Pharm. Era, Aug. 17, 1905, pp. 150, 151; Proc. Amer. Pharm. Assoc., 

vol. 54, 1906, p. 794. 

1905. Cascara Sagrada, Method of Gathering and Curing in Oregon, by J. 

Lee Brown. Western Druggist, Nov., 1905, p. 701 ; Proc. Amer. 
Pharm. Assoc., vol. 54, 1906, p. 794. 

1906. Cascara Sagrada, Fluidextract, U. S. P., Alcohol in, by Joseph Feil. 

Proc. Ohio State Pharm. Assoc., 1906, p. 48; Proc. Amer. Pharm. 
Assoc., vol. 55, 1907, p. 657. 
1906. Rhamnus Purshiana, Wild Medicinal Plants of the U. S., by Alice 
Henkel. Bureau of Plant Industry, U. S. Dept. Agri., Bui. 89, 
. 1906, p. 58. 

1906. Cascara Sagrada, Tasteless Preparation of, by H. Knopf. Chem. 

Ztg., vol. 30, p. 565 ; Pharm. Jour., Dec. 29, 1906, p. 723 ; Proc. 
Amer. Pharm. Assoc., vol. 55, 1907, p. 812; Jahresbericht der Pharm., 
vol. 41, 1906, p. 86. 

1907. Cascara Sagrada, Note on Fluidextract of, by C. Symes. Amer. 

J)rug., vol. 55, 1907, p. 77; Chem. Absts., vol. 3, p. 2341; Pharm. 
Zlg., vol. 54, 1909, p. 644 ; Jahresbericht der Pharm., vol. 44, 1909, 
P- 338. 

1907. Cascara Sagrada, Bitterless, Effect of Magnesia not Detrimental, by 



412 



Rhamnus Purshiana. 



( Am. Jour. Pharni. 
\ September, 1914. 



Caesar and Loretz. Herbstbericht, 1907; Pharm.' Ztg., vol. 52, 1907, 
p. 778; Proc. Amer. Pharm. Assoc., vol. 56, 1908, p. 246. 

1907. Cascara Sagrada, Improved Formula for Liquidextract of, by J. H. 

Franklin. Trans. Brit. Pharm. Conf. (Yearbook of Pharm.), 
1907, pp. 433, 434; Proc. Amer. Pharm. Assoc., vol. 56, 1908, p. 84. 

1907. Cascara Sagrada, Fluidextract of, Inefficiency of Identity Test G. P. 

IV, by H. Kroeber. Pharmac. Praxis, No. 11, 1907; Pharm. Ztg., 
vol. 53, 1908, p. 99; Proc. Amer. Pharm. Assoc., vol. 56, 1908, p. 84. 

1907. Cascara Evacuant, a Preparation, by Parke, Davis and Company. 

Amer. Jour. Pharm., vol. 79, 1907, p. 117. 

1908. Cascara Sagrada, Forest Trees of Pacific Slope, by Geo. B. Sudworth. 

Forest Service Bulletin, 1908, p. 404, U. S.^Dept. of Agri. 
1908. Rhamnus Purshiana, Description of Bark, by Dr. Henry Kraemer. 

Botany and Pharmacognosy, 3rd ed., 1908, p. 524. 
1908. Cascara Sagrada, Fluidextract of, Microscopic Method of Distinction 

from Fluidextract of Rhamnus Fragula, by R. Reutsh. Pharm. 

Post, No. 24, 1908; Pharm. Ztg., vol. 53, 1908, p. 278; Proc. Amer. 

Pharm. Assoc., vol. 56, 1908, p. 85. 
1908. Cascara Sagrada, Liquidextract of, Modification of B. P. Process, by 

F. Goldby. Pharm. Jour., Dec. 26, 1908, p. 838 ; Proc. Amer. Pharm. 

Assoc., vol. 57, 1909, p. 79. 
1908. Cascara Sagrada, Tasteless Liquidextract of, New Formula, by Ernest 

Quant. Amer. Jour, of Pharm., vol. 80, Nov., 1908, p. 524; Trans. 

Brit. Pharm. Conf. (Yearbook of Pharm.), 1908, pp. 519-21; Proc. 

Amer. Pharm. Assoc., vol. 57, 1909, p. 80. 

1908. Rhamnus Purshiana, Comparative Studies of the Bark with Rhamnus 

Frangula, by A. Tschirsch and J. F. A. Pool. Archiv. Pharm., 
vol. 246, pp. 315-25; Chemical Abstracts, vol. 3, p. 473. 

1909. Cascara Sagrada, Cultivation of, by R. H. True and G. F. Klugh. 

Proc. Amer. Pharm. Assoc., vol. 57, 1909, p. 824. 
1909. Cascara Sagrada, Bitterless Water Soluble Extract of, by Dr. M. Pen- 
shuck. Pharm. Ztg., vol. 54, 1909, p. 149; Chemical Abstracts, vol. 
3, p. 1796- 

1909. Cascara Sagrada, Tasteless Extract of, Patented in Germany, by 

Dr. Max Penshuck. Druggists' Cir., April, 1909, p. 183; Chemical 

Abstracts, vol. 5, March, 191 1, p. 973. 
1909. Rhamnus Purshiana, Fluidextract of, by L. Krober. Apoth. Ztg., 

vol. 24, 1909, pp. 307-308; Proc. Amer. Pharm. Assoc., vol. 57, 1909, 

p. 80. 

1909. Rhamnus Purshiana, American Medicinal Barks, by Alice Henkel. 

Bulletin 139, Bureau of Plant Industry, U. S. Dept. of Agriculture. 
1909. Cascara Sagrada, Fluidextract of, Use of Ammonia in, by C. Symes. 

Amer. Jour, of Pharm., vol. 81, October, 1909, p. 490; Trans. Brit. 

Pharm. Conf. (Yearbook of Pharmacy), 1909, pp. 319-20; Proc. 

Amer. Pharm. Assoc., vol. 58, 1910, p. 86. 
1909. Cascara Sagrada, Yellow Volatile Constituent, by F. H. Alcock. 

Phar. Jour, and Pharmacist, Nov. 27, 1909, p. 666; Proc. Amer. 

Pharm. Assoc., vol. 58, 1910, p. 218. 



Am. Jour. Pharm. ) 
September, 1914. J 



Rhamnus Purshiana. 



413 



1909. Cascara Sagrada, Preparation of Bitterless Extract by Use of Zinc 

Oxide. Jour, de Pharm. d'Anvers; Pharm. Ztg., vol. 54, 1909, p. 
594; Proc. Amer. Pharm. Assoc., vol. 58, 1910, p. 80. 

1910. Rhamnus Purshiana, Characters of Identity of Fluidextract, by L. 

Kroeber. Pharm. Praxis, 1910, No. 1 ; Pharm. Ztg., vol. 55, 1910, 
p. 376; Z. Oesterr. Apoth. Ver., vol. 49, p. 16; Proc. Amer. Pharm. 
Assoc., vol. 58, 1910, p. 86; Chemical Abstracts, vol. 5, p. 2696. 
1910. Cascara Sagrada, Bark Introduced in 1872 by Donnelly, by J. W. 

Forbes. Practical Druggist, Aug., 1910, p. 48; Chemical Absts., 
vol. 5, 191 1, p. 2696. 

1910. Cascara Sagrada, Wine Prepared from Bitterless Fluidextract of, by 

Dr. B. Borner. Apoth. Ztg., vol. 25, 1910, p. 591. 

191 1. Cascara Sagrada, Aromatic Fluidextract of, New Formula and Proc- 

ess, by R. C. Cowley. Chem. and Drug., July 22, 191 1, p. 46; Proc. 
Amer. Pharm. Assoc., vol. 59, 191 1, p. 59; Chemical Absts., vol. 
6, p. 411. 

191 1. Cascara Sagrada, Bitterless Fluidglycerate, by G. M. Beringer. Drug- 
gist Circular, May, 191 1. 

191 1. Cascara Sagrada, Bitterless Extract of, Use of Zinc Oxide. Pacific 
Drug Review, Aug., 191 1. 

191 1. Cascara Sagrada, Preparation of Bitterless Extract and Fluid- 
extract, by Dr. B. Borner. Proc. Amer. Pharm. Assoc., vol. 59, 
191 1, p. 60. 

191 1. Cascara Sagrada, Identification by Method of Pyro-analysis, by L. 

Rosenthaler. Proc. Amer. Pharm. Assoc., vol. 59, 191 1, p. 149. 

1912. Cascara Sagrada, Preparation of Fluidextract of. Apoth. Ztg., vol. 

2 7, PP- 32i~3i ; Chemical Absts., vol. 6, p. 1953. 
1912. Cascara Sagrada, Culture of, Pharmacal Plants and their Culture, by 
Dr. Albert Schneider. California State Board of Forestry, Bul- 
letin 2, pp. 42, 141. 

1912. Cascara Sagrada, Perestaltin, by Tschirsch and Monikowski. (Arch. 

der Pharm.) Druggists' Cir., Sept., 1912, p. 517. 
1912. Rhamnus Purshiana, The Medullary Ray Cells in, by Dr. H. Kraemer. 

Amer. Jour, of Pharm., vol. 84, 1912, p. 385; Chemical Absts., vol. 

6, p. 3160. 

1912. Cascara Sagrada, Apparatus for Estimation of the Extract of, by 
E. Biittner. Sudd. Apoth. Ztg., vol. 52, p. 271 ; Chemical Absts., 
vol. 6, p. 1818. 

1912. Cascara Sagrada, Preparation of Purified Extract of, by Diefenbach. 

Apoth. Zeit., vol. 26, p. 1046; Chemical Absts., vol. 6. p. 913. 

1913. Cascara Sagrada, Crude Botanical Drugs, by R. H. True. Pharm. 

Era, Jan., 1913, p. 9. 

1914. Rhamnus Purshiana and Rhamnus Californica, The Medullary Ray 

Cells in, by Oliver A. Farwell. Jour. Amer. Pharm. Assoc., vol. 
3, May, 19 14, p. 649. 

University of Washington, College of Pharmacy, 
Seattle, Washington, June 17, 1914. 



414 Insecticidal Value of Larkspur Seed. { A s ™ pt eXer P i9iT' 

THE INSECTICIDAL VALUE OF FLUIDEXTRACT OF 
LARKSPUR SEED.* 

By J. B. Williams. 

An examination of several samples of fluidextract of larkspur 
seed on the market at the present time showed a very marked dif- 
ference in their physical, chemical, and insecticidal properties. The 
samples examined varied in color from a dark brown to a very light 
yellow ; the alcoholic content from 40 per cent, to 80 per cent., the 
fixed oil content from less than 0.2 per cent, to nearly 20 per cent., 
the alkaloidal strength from 0.43 per cent, to over 1 per cent., while 
the insecticidal value varied 500 per cent. (1 to 5). 

With the object in view of determining if possible the constit- 
uent of larkspur seed to which it owes its insecticidal properties, 
and the best means of extracting the same, a number of fluidextracts 
were prepared, using various menstrua. The resulting fluidextracts 
were assayed for alkaloidal content and also for fixed oil, and their 
insecticidal value was determined by tests on living insects (bedbugs). 
The seed used was that of DeipJiiniuni ajacis, L., and was ground to 
a No. 30 powder. The methods of extraction were as follows : 

•No. 1. — Extracted by percolation with 95 per cent, alcohol, the 
strong percolate reserved and extraction continued until the drug was 
practically exhausted ; the weak percolate evaporated to a soft extract 
and dissolved in the reserved portion, and sufficient 95 per cent, 
alcohol added to make 1 c.c. for each gramme of drug used. Upon 
standing this fluid separated into two well-defined layers, the upper 
oily layer equalling about 45 per cent, and the lower layer about 55 
per cent, of the whole. These were separated and each made up to 
the original volume with 95 per cent, alcohol and, for purposes of 
identification, marked i-A for the upper and i-B for the lower 
layer. 

No. 2. — Extracted by percolation in usual manner with dilute 
alcohol. 

No. 3. — Extracted with 30 per cent, alcohol. 

No. 4. — Extracted with petroleum benzine, the benzine removed 



* Presented at the meeting of the American Chemical Society at Rochester, 
N. Y., September, 1913. 



A s™ptemberf i9iT' } Insecticidal Value of Larkspur Seed. 415 

by evaporation on the water-bath and the residue dissolved in 95 per 
cent, alcohol. 

No. 5. — Extracted with petroleum benzine, the benzine solution 
shaken out with dilute acid to remove the greater part of the alkaloid, 
then evaporated and the residue dissolved in 95 per cent, alcohol. 

No. 6. — Extracted with 10 per cent acetic acid, the acid removed 
by distillation and the residue dissolved in dilute alcohol. 

No. 7. — The drug residue from No. 6 extracted with 95 per cent 
alcohol. 

No. 8. — Extracted with 95 per cent, alcohol until a yield of 1 c.c. 
for each gramme of drug used was obtained. This gave a perfectly 
clear fluid, showing no signs of separating after standing several 
weeks. 

No. 9. — The extraction of drug residue of No. 8 continued until 
a further yield of 1 c.c. for each gramme of drug used was obtained. 

No. 10. — The alkaloidal residues of several assays dissolved in 
sufficient 95 per cent, alcohol to make a 1 per cent, solution. 

These fluidextracts varied in color from a dark brown (No. 6) to 
a very light yellow, and after standing several weeks, with the excep- 
tion of Nos. 2, 3, and 6, which show some sediment, are in good 
condition. 

The alkaloid and fixed oil contents are as follows : 



Color Alkaloid Oil 

f i— A Pale yellow 0.26 21.34 

\ i-B Yellow 0.81 7.08 

2 Dark brown 1.42 0.19 

3 Dark brown 1.26 0.12 

4 Pale yellow 0.17 30.37 

5 Pale yellow 0.06 30.54 

6 Very dark brown 1.24 0.14 

7 Yellow 0.06 23.67 

8 Yellow 0.60 24.76 

9 Pale yellow 0.11 3.60 

10 Reddish yellow 1.0 (not assayed) 



The drug itself assayed 1.78 per cent, alkaloids and 36.1 per cent. 

oil. 

The insecticidal values of the fluids were determined by Mr. H. 
C. Hamilton by the method of Houghton & Hamilton.* The results 
were as follows : 

* Eleventh Report of the Michigan Academy of Science, 1909. 



416 



Progress in Pharmacy. 



J Am. Jour. Pharm. 
) September, 1914. 



Effective dilution Coefficient. 



U-B .1-50 2.5 

2 1-18 0.9 

3 1-12 0.6 

4 1-120 . 6.0 

5 ...1-150 7.5 

6 1-18 0.9 

7 1-120 6.0 

8 i— 100 5.0 

9 1-15 0.75 

10 1-12 0.6 

11 standard...: 1-20 1.0 



From the above results it would appear that it is the oil and not 
the alkaloid to which larkspur seed owes its insecticidal properties, 
and, since the fluid is seldom used internally but almost exclusively 
as an insecticide, it would seem that the menstruum that will extract 
the largest amount of oil is the proper one to use. It should be noted, 
however, that the alkaloid has a slight insecticidal value, as the sample 
containing i per cent, of alkaloid and no oil was one-tenth as active as 
the samples containing a high content of oil. 

Analytical and Experimental Department, 
Parke, Davis & Co.. Detroit, Mich. 



PROGRESS IN PHARMACY. 

A Quarterly Review of Some of the More Interesting Litera- 
ture Relating to Pharmacy and Materia Medica. 

By M. I. Wilbert, Washington, D. C. 

The European war has precipitated a condition unprecedented 
and unparalleled in the history of the drug trade of this country, 
and has demonstrated as no other line of argument possibly could 
that we in America are still largely dependent on European countries 
for our supplies of drugs and chemicals. More than 50 per cent, 
of the drugs and chemicals used in pharmacy and allied industries 
has been subjected to marked advances in price. The available 
stocks of many articles of a staple nature appear to have been 
at a rather low level, and some of the chemicals of German origin 
are already practically exhausted. 

It will no doubt be months before the drug market can adjust 



Am. Jour. Pharru. ) 
September, 1914. J 



Progress in Pharmacy. 



417 



itself to the suddenly changed conditions, and the ultimate solu- 
tion of the problems that are now presented will be eagerly awaited 
by all. The influence that the changed conditions will have on 
American Pharmacy should be a beneficial one, as the present 
scarcity of articles that could be made will no doubt stimulate the 
growth of chemical industries in this country. 

Considerable concern has been expressed as to the whereabouts 
of the German-American apothecaries and their friends who in 
their trip through Europe reached Bremen on July 13. They were 
the guests of the Berlin apothecaries on July 15, 16 and 17. (Apoth- 
Ztg.j 1914, vol. 29, pp. 644-645, 657-658.) An elaborate program 
had been prepared for their entertainment, one day being spent at 
the pharmaceutical institute of the University of Berlin at Dahlen. 
The apothecaries of Vienna, Munich, and several of the other large 
cities in Germany, Austria, Switzerland, and France had also pre- 
pared elaborate programs for entertaining the American pharmacists, 
but their itinerary has no doubt been interrupted by the general 
disturbance on the continent. 

Friederich Mohr. — On June 21, 1914, there was unveiled in the 
city of Coblentz, Germany, a monument to one of the pioneers in 
pharmacy, Friederich Mohr, who despite the fact that he was the 
author of probably the original text-book on the practice of pharmacy 
is perhaps more widely known for his connection with the develop- 
ment of analytical chemistry than with that of galenical pharmacy. 
Pharmacists of an older generation will remember the book " Prac- 
tical Pharmacy " by Mohr and Redwood, an American edition of 
which, edited by Wm. Procter, Jr., was in its day generally referred 
to as Mohr, Redwood and Procter's pharmacy. Friederich Mohr 
was born in the city of Coblentz in 1806, was a student at Bonn, 
Berlin, and Heidelberg, a voluminous writer, and is frequently re- 
ferred to as the classic writer of pharmacy. His text-book of 
pharmaceutical technic was first published in 1847, ms text-book on 
titration methods in 1855, and a commentary on the first edition of 
the German Pharmacopoeia in 1874. Most of his life was spent in 
the pharmacy left him by his father and it was not until he reached 
his sixtieth year that he was called as a professor to Bonn, where 
he died in 1879. — Apoth.-Ztg., 1914, vol. 29, pp. 547-550. 

Before this copy of the Journal reaches its readers the meetings 
of the National Association of Retail Druggists and the American 
Pharmaceutical Association will have become history. From present 



4i8 



Progress in Pharmacy. 



( Am. Jour. Pharm. 
\ September, 1914. 



indications both of these meetings will be interesting, profitable 
and well attended. 

The American Chemical Society's summer or fall meeting, which 
was to have been held in the city of Montreal, Canada, September 
15th to 1 8th, has been indefinitely postponed because of the European 
war and the present outlook is that the next meeting of the American 
Chemical Society will be held in New Orleans, April ist to 3d, 191 5. 

U. S. P. Revision. — The fourth and fifth instalments of abstracts - 
of proposed changes with new standards and descriptions for the 
United States Pharmacopoeia, ninth revision, have been published. 
The first includes proposed proximate assays of crude drugs and 
galenical preparations and the latter embraces most of the biological 
products and volatile oils. The material so far published should 
prove a fruitful source for discussion at the Detroit meeting of the 
American Pharmaceutical Association. 

Official Assay Processes. — Dichgans, H., in concluding a com- 
parative examination of pharmacopceial methods for the assay of 
potent drugs and medicinal preparations, states that his results in- 
dicate that the directions for alkaloidal assay included in many of 
the pharmacopoeias are not at all suited to the purpose. The results 
obtained are in many instances variable, while in others the methods 
are so complicated that they are unsuited for general practice. The 
different methods when applied to the same material give widely 
variable results, indicating that uniformity in the content of potent 
drugs can be secured only when the method of assay adopted is 
uniform. 

Total Extractive as a Factor in Fluid Extract Manufacture. 
(Maines and Gardner.) — The determination of total extractive is 
an important factor in the manufacture of fluid extracts, especially 
those of the known alkaloidal drugs. A table of the total extractive 
determinations is given which represents estimations covering many 
years of work, and the products of several of the large manufactures. 
— /. Am. Pharm. Assoc., 1914, vol. 3, pp. 997-1000. 

Useful Drugs. (Report of the Board of Trustees.) — The work 
of the committee on a selected list of drugs has resulted in the publica- 
tion of the book called " Useful Drugs." This has already been 
adopted as a text-book by a number of our best schools ; its adoption 
has been considered by the State licensing boards, one already having 
adopted it, and there is every indication that this enterprise will have 
a most beneficial effect. — /. Am. M. Assoc., 1914, vol. 63, p. 75. 



A seFtemb r er P i9iT" } Progress in Pharmacy. 419 

Prescriptions. (Taylor, George B.) — A rep'ort on carelessness 
in the filling of simple prescriptions in the State of Louisiana. In 
December, 191 3, a prescription calling for 2 gm. of boric acid and 2 
ounces of distilled water was filled by 68 New Orleans druggists. 
Of these, 22, or 32.3 per cent., were correct both as to distilled water 
and to weight (some allowance is given in weight) ; 17, or 25 per 
cent., were correct as to weight but not as to the use of distilled 
water; 14, or 20.6 per cent., were correct as to distilled water but 
incorrect in weight; and 15, or 22.1 per cent., were incorrect both 
as to use of distilled water and as to weight. — Rep. Louisiana Bd. 
H., 1912, 1913, pp. 176-187. 

Weights and Measures. — In an address before the National Con- 
ference on Weight and Measures of Washington, D. C, Mr. F. P. 
Downing, chief inspector of weights and measures for the State of 
Wisconsin, referred to alleged inaccuracies in the delicate weighing 
apparatus in drug stores, jewelry stores, and the like. Coin weights 
used on such scales were stated by him to be often 10 to 30 per cent, 
light. In a recent inspection of drug stores in Milwaukee 22.1 per 
cent, of the dispensing scales and 43.6 per cent, of the dispensing 
weights in use were found in error. — Pharm. J., 1914, vol. 92, p. 905. 

Food and Drugs Law. — An important interpretation of the pure 
food and drugs act was handed down on June 13, by the United 
States Circuit Court of Appeals at Cincinnati in the case of the 
United States vs. Forty Barrels and Twenty Kegs of coca cola, 
which reads in part as follows : The general purpose and intent must 
be deemed to be the prevention of fraud and deception, so that the 
purchaser can get the thing he has a right to suppose he is getting, 
rather than the protection of the public health to the extent of pre- 
venting the purchaser from deliberately and intentionally buying a 
particular food which is what it purports to be, even though a jury 
might think it " deleterious. " — Druggists' Circular, 1914, vol. 58, 
p. 487. 

The Patent Medicine Business. (News Note.) — Dr. S. S. Gold- 
water, commissioner of health of New York City, has announced 
that a systematic investigation of the patent medicine business would 
be begun at once. It is proposed to insist that the manufacturer of 
a patent medicine name the ingredients in the mixture and it is be- 
lieved that public opinion is sufficiently enlightened to support this 
movement. — /. Am. M. Assoc., 1914, vol. 63, p. 411. See also Drug- 
gists' Circular, 191 4, vol. 58, p. 481. 



420 



Progress in Pharmacy. 



( Am. Jour. Pharm. 

t September, 1914. 



Patent Medicines. {Anon.) — -Our Parliamentary correspondent 
learns that a further prolonged sitting of the Select Committee on 
Patent and Proprietary Medicines was held on Tuesday at the House 
of Commons. Sir Henry Norman, the Chairman, again presided. 
Altogether, the meeting lasted for some hours, and, as the result, 
about one-half of the draft report has now been disposed of. — Chem. 
and Drug., 1914, vol. 85, p. 223. 

Consumption Cure. (Editorial.) — After a hearing extending 
over seven days, the libel action against the British Medical Associa- 
tion brought by Mr. C. H. Stevens, the proprietor of " Stevens' 
Consumption Cure," has terminated in a verdict for the defendants. 
The jury, after an absence of about 10 minutes, found the matter 
complained of was of the nature of fair comment and judgment was 
accordingly given in favor of the British Medical Association. — 
Pharm. J., 1914, vol. 93, p. 191. 

Proprietary Remedies. (Editorial.) — The drug fund of the 
London Insurance Committee is threatened by the over-prescribing 
of proprietaries and the drugs and appliances sub-committee of the 
Insurance Committee has issued a list of articles as not being 
" proper and sufficient drugs and medicines and prescribed ap- 
pliances required to be provided for insured persons," under the 
National Insurance Act. — Chem. and Drug., 1914, vol. 85, p. 221. 

National Insurance Pharmacopoeia. — kt Karshish " suggests the 
adoption of a national insurance pharmacopoeia to avoid unnecessary 
deficiencies in the drug fund. — Pharm. J., 1914, vol. 93, p. 11. 

British Pharmacopoeia. (London Letter.) — The work of prepar- 
ing a new edition of the British Pharmacopoeia has now been com- 
pleted. One of the chief features will be that limits of impurity in 
drugs and medicinal chemicals — especially dangerous impurity — 
will be carefully defined. Another feature of the book is an ex- 
tension of chemical standardization to drugs not at present standard- 
ized, but there is no recognition of physiologic standardization. 
The international unification of the quality of preparations of potent 
drugs, which has received the endorsement of various nations, has due 
recognition in the forthcoming book. — /. Am. M. Assoc., 1914, vol. 
62, p. 2039. 

British Pharmacopoeia. (Editorial.) — At its meeting on July 13 
the Executive Committee of the General Medical Council formally 
adopted the completed draft of the British Pharmacopoeia, 1914, as 
submitted by the Pharmacopoeia Committee. It was resolved that 



Am. Jour. Pharm. ) 
September, 1914. j 



Progress in Pharmacy. 



421 



copies in advance of publication should be made accessible to the 
public for inspection at the offices of the Council in London, Edin- 
burgh, and Dublin on Monday, August 10. The official publication 
of the Pharmacopceia will be made in the London Gazette on Friday, 
October 9, on which day copies will be on sale at the publishers. — 
Pharm. J., 1914, vol. 93, p. 78. 

British Pharmaceutical Conference. — The 51st annual meeting 
of the British Pharmaceutical Conference was held at Chester, July 
20 to 25, 1914, presided over by Edward H. Farr, who chose for 
the subject of his presidential address a discussion of recent work 
on plant products. The proceedings are reported at length in the 
British pharmaceutical journals for July 25, 1914, and the papers 
presented are published in the journals of the same date. The total 
number of papers presented was 28, of which 25 were read in the or- 
dinary section and 3 in the practice section. The nature of these 
communications was well up to the average and should prove to be of 
interest to all who are in any way engaged in the practical side of 
their profession. — Pharm. 1914, vol. 93, pp. 1 17-139; also Chem. 
and Drug., 1914, vol. 85, pp. 161-195. 

The papers read in the ordinary section of the British Pharma- 
ceutical Conference included the following: 

Estimation of Strychnine in the Presence of Brucine. (Ditt, 
D. B.) — A modification of Gordon's process is recommended, the 
experimental data recorded showing that the use of 1 c.c. of con- 
centrated nitric acid for each 0.25 Gm. of brucine in the propor- 
tion of 1 to 10 volumes of acid solution, made for a period of 20 
minutes at ordinary temperature, is quite sufficient to destroy all 
the brucine. — Pharm. J ., 191 4, vol. 93, p. 120. 

The Purity of Pepsin Bacteriologically Considered. (Quant 
Ernest.) — A report on 11 samples of pepsin from various sources, 
only two of which were free from micro-organisms. The author 
suggests that the product may be improved by the presence of free 
acid and the use of chloroform. — Pharm L, 1914, vol. 93, pp. 120, 121. 

The Adulteration of Belladonna Leaves. (Allen and Deane.) — 
The leaves of Phytolacca decandra, Scopola carniolica, and Ailan- 
thus glandulosa were found admixed with commercial belladonna 
from Continental sources to the extent of from 20 to 80 per cent. 
The authors review the literature and present a number of illustra- 
tions showing the macroscopic and microscopic features of the 



422 



Progress in Pharmacy. 



f Am. Jour. l'harm. 
1 September, 1914. 



several substitutes compared with the distinguishing features of 
the genuine drug. — Pharm. J. } 1914, vol. 93, pp. 121-123. 

The Rate of Dialysis of Alkaloids in Aqueous Solution and 
in the Form of Galenicals. (Finnemore, H.) — From experiments 
reported the author 'concludes that strychnine in aqueous solution 
diffuses more rapidly than in the form of the liquid extract of nux 
vomica, and this fact may have some bearing on the therapeutic 
effect of the two. — Pharm. J., 1914, vol. 93, pp. 123, 124. 

The Incompatibility of Strychnine and Nux Vomica with Alka- 
lies, Iodides, and Bromides. (Finnemore and Williamson.) — The 
most striking feature of the experiments now recorded is the dif- 
ference in the behavior towards alkalies of strychnine in the form 
of the solution and that existing in its natural state in admixture 
or combination with the other ingredients of nux vomica seeds. 
It appears that, whereas strychnine and alkalies or iodides may 
become dangerous under varied and indeterminate conditions, when 
the drug is given in the form of the tincture or the liquid extract 
no precipitation occurs and no danger need be apprehended, pro- 
vided the concentration is not greater than that found under normal 
conditions of prescribing and dosage. 

The Analytical Characters of Benzoin. (Cocking and Kettle.) — 
The alcohol soluble matter in benzoin is not readily determined 
directly, owing to the volatility of the balsamic constituents, and the 
easiest way is to obtain it by exhausting the drug by alcohol. A 
modified method for the determination of the aromatic acid is sug- 
gested, and a table showing the composition of a number of the 
commercial samples of the drug is included with the paper. — Pharm. 
J.. 1914, vol. 93, pp. 125, 126. 

The Mineral Constituents of Certain Tinctures and Drugs. 
(Lewis, S. Judd. ) — The molecular structure of chlorophyll is very 
closely related to haematin, the red coloring matter of the blood. 
The former, under the influence of -light, brings about the absorp- 
tion of carbon dioxide by plants and the elimination of oxygen, 
and has magnesium as an essential element, hence magnesium is 
to be anticipated in all mineral matter which has passed through 
the vegetable cell. The presence of iron is also necessary for the 
formation of chlorophyll, although it does not enter into the con- 
stituents of the pigment. Potassium and calcium are also con- 
stantly present, and the occurrence of other metals is frequently 
more or less accidental. Sodium is widely distributed, while lithium, 



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September, 1914. / 



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423 



aluminum and manganese are rarely encountered. Copper is not rare. 
Among the non-metals, sulphur and phosphorus are nearly always 
present in the ashes of plants. — Pharm. J., 1914, vol. 93, pp. 126-128. 

The Stability of Cinnamic Aldehyde. (Phillips, H. Adie.) — 
It has been contended that in the distillation of the oil from chips 
there was a likelihood that some of the cinnamic aldehyde was 
oxidized to cinnamic acid. The experiments reported seem to prove 
that under the usual conditions prevailing under steam distillation 
cinnamic aldehyde, both pure and as a constituent of cinnamon oil, 
is not appreciably oxidized. — Pharm. J., 1914, vol. 93, pp. 129, 130. 

The Composition of Tinctura Iodi Decolorata. (Pratt, Walter 
R.) — The finished tincture made according to the directions of the 
British Pharmaceutical Codex is an alcoholic solution of ammonium 
iodide, with excess of ammonia containing about 0.1 per cent, 
iodoform and in some cases ammonium iodate, hydroxylamine, and 
acetaldehyde. — Pharm. J., 1914, vol. 93, pp. 130, 131. 

The Determination of Iron in the Presence of Phosphoric Acid. 
(Corfield and Pratt.) — The gravimetric determination of ferric iron 
in the presence of even small quantities of phosphates gave results 
which are much too high and are variable among themselves. Both 
the idiometric and reduction by stannous chloride volumetric meth- 
ods give results which are very accurate and can be equally well 
used in the presence of phosphoric acid. The former method gives 
results which tend to be somewhat high. — Pharm. J., igi4, vol. 
93. PP- I3T-I33- 

An Improved M ethod for the Administration of Extr actum Filicis 
Maris Liqnidum. (Crossley, Holland F. W.) — Oleoresin of as- 
pidium can best be exhibited in the form of a jelly made with gelatin 
and glycerin, sweetened with saccharin and flavored with oil of cin- 
namon. This form of preparation is said to be more palatable than 
emulsions or capsules, and the bulk is reasonable in relation to the 
dose. — Pharm. J., 1914, vol. 93, p. 133. 

The place of Carbon Bisulphide in Official Pharmacy and Sug- 
gestion for its Further Use. (Alcock, F. H.) — The use of carbon 
disulphide is recommended as a solvent for fats and as a means for 
ascertaining the amount of constituents extractable from official liquid 
preparations, such as liquid extracts and tinctures. Some useful 
results have been obtained, a number of which are recorded. — 
Pharm. ./., 1914, vol. 93, pp. 133, 134. 

The Composition of the Glycerophosphates of Commerce. (Um- 



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f Am. Jour. Pharm. 
\ September, 1914. 



ney and Bennett.) — Calcium glycerophosphate is of variable com- 
position and does not contain a definite proportion of water. Potas- 
sium glycerophosphate is not readily obtainable in a crystalline form, 
and the crystalline form of sodium glycerophosphate contains 5 
molecules of water. Magnesium glycerophosphate is rendered more 
soluble by the presence of citric acid, and no definite formula for 
the hydrated salts can be given. Ferric glycerophosphate should 
contain approximately 15 per cent, of metallic iron and should be 
completely soluble in two parts of water.— Pharm. /., 1914, vol. 93, 
PP- 134. 135- 

Commercial Standards for Dried Magnesium Sulphate, Sodium 
Sulphate, and Sodium Phosphate. (Umney and Bennett.) — A rea- 
sonable standard for dried magnesium sulphate would be that it 
should be prepared by drying at ioo° until it has lost about one-third 
of its weight, and that the product should contain not less than 23 
per cent, and not more than 31 per cent, of water. It should be com- 
pletely and readily soluble in water. Sodium sulphate should be 
practically anhydrous and should not contain more than 5 per cent, 
of water. For sodium phosphate 5 per cent, of water would be a 
reasonable limit. — Pharm. J., 1914, vol. 93, pp. 135, 136. 

Liquor Opii Sedativus. (Bennett and Cocking.) — Suggestions 
to improve the formula included in the British Pharmaceutical 
Codex. The opium should be exhausted by cold maceration in lime 
water, and the solution should be subsequently but slightly acidified 
by hydrochloric acid or sulphuric acid, after the addition of alcohol 
and wine. — Pharm. J., 1914, vol. 93, pp. 136, 137. 

Some Uses of a Tincture Press. (Pollard, E. W.) — An illus- 
trated description of possible uses of a tincture press as a pill-piper 
or as a suppository machine. — Pharm. J., 1914, vol. 93, pp. 137, 138. 

Anccsthetic Ether of Commerce. (Finnemore, H.) — -An exami- 
nation of a number of samples of ether in actual use shows that, 
while some samples may have been rather inferior, in the main they 
have reached a fair average of purity. The impurities found consist 
of acetone, water, alcohol, acetaldehyde, peroxides, and acids. — 
Pharm. J., 1914, vol. 93, pp. 138, 139. 

Medical Museum. (Anon.) — The Wellcome Historical Medi- 
cal Museum in London was reopened on May 28, 19 14, in a per- 
manent home, 54 A, Wigmore Street, Cavendish Square, London, 
W. The museum is open daily from 10 a.m. to 6 p.m., Saturdays 
to T p.m. Members of the medical profession and related callings 



^pteXerfmT-} Progress in Pharmacy. 425 

are admitted on the presentation of their visiting cards. — Sudd. 
Apoth.-Ztg., 1914, vol. 54, p. 403. 

The Hague Opium Conference. — The third conference of rep- 
resentatives of the Powers for the purpose of regulating the produc- 
tion and distribution of opium, morphine, and cocaine and their 
derivatives was held at The Hague, June 23 to 25, 19 14. It was con- 
cluded to be possible to put the convention into force notwithstanding 
the fact that some Powers have as yet not signed the convention in 
compliance with Article 23. — Oil, Paint and Drug Rep., 1914, vol. 
86, July 20, p. 18. 

Opium Suppression. (Editorial.) — The difficulty of inducing an 
Oriental nation to do without some narcotic, and the danger of opium 
smoking being superseded by the still worse habits of cocaine and 
morphine injection, have long been noted. In the course of a recent 
trial it was stated that during the past two months about 200 pounds 
of morphine had been seized by the customs officials at Shanghai. — 
Pharm. J., 1914, vol. 93, p. 78. 

Opium Habit. — In answer to an inquiry the Secretary of State 
for the Colonies admits that it is the fact that the consumption of 
fermented liquors, especially beer and stout, had considerably in- 
creased in the Malay States since 1909, and the working of the Excise 
Enactments is being carefully studied with a view to the proper con- 
trol of this consumption. — Pharm J., 1914, vol. 93, p. 50. 

The Harrison Anti-narcotic Bill was finally agreed to by the 
Senate on the afternoon of Saturday, August 15, in a form that will 
undoubtedly make it acceptable to members of the House and to 
the President. 

Smoking Opium. — In May last the Commissioner of Internal 
Revenue made a decision regarding aqueous extract of opium, in 
which it was stated that, while this product may have some medicinal 
uses, such uses may be covered by the use of powdered extract of 
opium ; also it is stated that the aqueous extract of opium is used to 
a considerable extent by opium smokers and is suitable for that pur- 
pose. Under the decision, the manufacturers of this product are 
required to comply with the law as to smoking opium. Taking up 
this subject, the Treasury Department has issued a decision calling 
attention to the action of the Commissioner of Internal Revenue, 
and stating that this product is within the scope of the smoking 
opium Jaw passed on January 17, 1914, which prohibits the impor- 
tation of such opium, and the collectors of customs are required to 



426 



Progress in Pharmacy. 



( Am. Jour. Pharm. 

I September, 1914. 



refuse delivery of aqueous extract of opium and to return the impor- 
tation to the country whence it came. — Druggists' Circular, 1914, 
vol. 158, p. 487. 

Boylan Law. (A News Note.) — After an unavoidable delay in 
printing them, due to the failure of the State Legislature to make 
an appropriation therefor, the Boylan law order blanks, which must 
now be used by all pharmacists, druggists, physicians, dentists, and 
veterinarians in New York State, when buying opium and chloral, 
their derivatives and preparations containing the same, are now 
being distributed. — Oil, Paint and Drug Rep., 19 14, vol. 86, July 6, 
p. 11. 

Death by Poisoning in Great Britain. — The 75th annual report of 
the Registrar-General of Births, Deaths, and Marriages in England 
and Wales shows that the number of deaths due to poisons and 
poisonous substances in 1912 was neither materially larger nor 
smaller than the average for recent years. The number of deaths 
certified as due to accidental poisoning by scheduled poisons was 
122, against 124 in 191 1, and by non-scheduled substances 102, against 
115 in 191 1. The number of cases in which poisons were taken by 
suicides was 547 (347 scheduled and 200 non-scheduled) ; in the 
previous year scheduled poisons were used in 324 cases, and non- 
scheduled in 195. — Phar. J., 1914, vol. 93, p. 3. 

Responsibility for Poisoning. (Anon.)- — The responsibility for a 
fatal and an additional serious case of poisoning by impure barium 
sulphate, used in the course of a Rontgen-ray examination at Prague, 
has finally been fixed by the upper court at Vienna. This court decided 
that the pharmacist in charge of the pharmacy was responsible and 
guilty of neglect because of his having failed to carefully examine 
the barium sulphate before allowing it to be dispensed or used. The 
assistants in the pharmacy and in the wholesale drug establishment 
from which the barium sulphate had been purchased were freed, 
despite the objection made by the State's Attorney. — Siidd. Apoth- 
Ztg., 1914, vol. 54, p. 403. 

Studies on the Absorption of Drugs. (Hatcher and Eggleston.) — 
A summary of observations on the absorption of drugs, with the con- 
clusion that the ratio of absorption from the four common channels 
of administration differs for each drug. No rule can be formulated 
for the calculation of the appropriate dose by one mode of admin- 
istration from the dose by any other mode of administration. Such 



Am. Jour. Pharm. ) 
September, 1914. J 



Progress in Pharmacy. 



427 



determination can be made only by experiment. — /. Am. M. Assoc., 
1914, vol. 63, pp. 469-473- 

Algocratine. — Mannich and Leemhuis, from the pharmaceutical 
laboratory of the University of Gottingen, report an examination 
of a powder offered as an infallible remedy for migraine, neuralgia, 
grippe, influenza, and other diseases. The preparation was found 
to consist essentially of a mixture of 50 Gm. phenacetin, caffeine 10 
Gm.j and pyramidon 40 Gm. The claims made for the composition 
of the preparation were found to be quite untrue. — Apoth.-Ztg., 
1914, vol. 29, p. 553. 

Antimeningitis Serum. (Auer, John.)